Warning: I have almost no knowledge of biology past the high school level.
Viruses generally have three components: the DNA, the virus protein coat, and an outer membrane "decorated" with these surface marker glycoproteins. I am thinking that a virus would want to infect as many hosts as possible, so that it would reproduce as much as possible, why would a virus just infect one group of organisms.
What evolutionary advantage do viruses have in host specificity?
It is true for any living creature, that it would be great for it if it could thrive in all environments. Any creature would do better if it had a greater ecological niche while remaining as competitive in each of these niches. However, competition, predation and other biotic and abiotic factors lead species to specialize in specific niches. Of course, some species are more generalist and some are more specialist but I won't go into these details.
When it comes to parasites, such as viruses, the story is the same. A host is an environment. Being less specific would be great but the immune system is no easy detail to get around. Viruses are often quite specific to a given species, just because it evolved to be efficient for a given host but tend not to be that efficient in other hosts.
Note that parasites are not only species specific but also often tissue specific and specific to the specifics genetics of the host (e.g. malaria).
Somewhat related posts:
Thank you @DeNovo for helpful comment
I would more specifically address the advantage/benefit, in that even though a virus may be host specific (or not, since it really doesn't matter in terms of gain), even the most virulent of viruses throughout history have not killed off entire species, save the 'virus' of being man (whole other story), yet for some reason some within a species survive! They may have a specific protein, are a carrier - the list is long and not entirely understood. In any case, they often handoff whatever adaptable mutation they have to their offspring, thereby making them immune to such viruses. Survival of the fittest?
In biology and medicine, a host is a larger organism that harbours a smaller organism  whether a parasitic, a mutualistic, or a commensalist guest (symbiont). The guest is typically provided with nourishment and shelter. Examples include animals playing host to parasitic worms (e.g. nematodes), cells harbouring pathogenic (disease-causing) viruses, a bean plant hosting mutualistic (helpful) nitrogen-fixing bacteria. More specifically in botany, a host plant supplies food resources to micropredators, which have an evolutionarily stable relationship with their hosts similar to ectoparasitism. The host range is the collection of hosts that an organism can use as a partner.
The adaptation of codon usage of +ssRNA viruses to their hosts
Viruses depend on their host's cellular structure to survive. Most of them do not have tRNAs, their translation relies on hosts' tRNA pools. Over the course of evolution, viruses needed to optimally exploit cellular processes of their host. Thus, codon usage of a virus should coevolve with its host to efficiently and rapidly replicate. Some viruses can invade a broad spectrum of hosts (BSTVs), while others can invade a narrow spectrum only (NSTVs). Consequently, we test the hypothesis that similarity of codon usage preference and the degree of matching between BSTVs and their hosts will be lower than that of NSTVs, which only need to coevolve with few hosts. We compare the patterns of codon usage in 255 virus genomes to test this hypothesis. Our results show that NSTVs have a higher degree of matching to their hosts' tRNA pools than BSTVs. Further, analysis of the effective number of codons (ENC) infers that codon usage bias of NSTVs is relatively stronger than that of BSTVs. Thus, codon usage of NSTVs tends to better match their host than that of BSTVs. This supports the hypothesis that viruses adapt to the expression system of their host(s).
Keywords: Adaptability Codon usage patterns Expression system Host Virus tRNA pool.
Copyright © 2018 Elsevier B.V. All rights reserved.
Matching degree (MD) of viruses…
Matching degree (MD) of viruses to their hosts' tRNA pools. (a) Group 1…
Similarity of overall codon usage…
Similarity of overall codon usage pattern of viruses to their hosts. (a) Group…
Effective number of codons (ENCs)…
Effective number of codons (ENCs) of 20 virus genera. (a) BSTVs and NSTVS.…
A virus attaches to a specific receptor site on the host cell membrane through attachment proteins in the capsid or via glycoproteins embedded in the viral envelope. The specificity of this interaction determines the host—and the cells within the host—that can be infected by a particular virus. This can be illustrated by thinking of several keys and several locks, where each key will fit only one specific lock.
Link to Learning
This video explains how influenza attacks the body.
How viruses mutate and create new variants
“A virus will make hundreds to thousands of copies of itself every time it is in a cell,” says Marta Gaglia. “The chances of getting a mutant is high just because there’s so many replications happening.” Here, the Alpha variant virus. Credit: NIAID
As the COVID-19 pandemic continues, new variants of the SARS-CoV-2 virus pop up, and some lead to increasing infections. The main new variants—named Alpha, Beta, and Gamma and first identified in Britain, South Africa, and India, respectively—have properties that make them more successful in transmitting and replicating than the original virus.
A recent report, for instance, shows that the Alpha variant, which is now the dominant variant in the United States, works by disabling the immune system's first line of defense, interferon cells, which signal the body to attack viruses.
Viruses are not technically living things—they invade living cells and hijack their machinery to get energy and replicate, and find ways to infect other living organism and start the process over again.
How viruses mutate largely has to do with how they make copies of themselves and their genetic material, says Marta Gaglia, an associate professor of molecular biology and microbiology at the School of Medicine. Viruses can have genomes based on DNA or RNA—unlike human genomes, which are made up of DNA, which then can create RNA.
Gaglia studies how viruses take control of infected cells and reprogram the cells' machinery to reproduce themselves. "We've been working on a protein that the virus encodes that destroys the host RNA, blocking the cells from being able to express their own protein and blocking, among other things, antiviral response," she says.
Tufts Now talked with Gaglia to learn more about how different viruses mutate and what it might mean for the COVID-19 virus and vaccines' ability to stop its transmission.
Tufts Now: What is the difference between a DNA-based virus and an RNA-based virus?
Marta Gaglia: The main difference is that the genome can be a molecule of DNA or a molecule of RNA. Our genome and the genome of all cellular organisms is always DNA, but viruses can either encode their genome as DNA or RNA. Coronaviruses like SARS-CoV-2 are RNA-based viruses.
Can you briefly explain the difference between DNA and RNA?
They're very similar molecules. DNA is almost always double stranded, and each of the sugars has a base attached: adenine (A), cytosine (C), guanine (G), and thymine (T). The A, C, G, and T pair up with each other that makes it very stable as a molecule.
RNA is a similar molecule. Most often, it's single-stranded. And one of the bases is different—it's uridine versus thymine—but roughly speaking, it is the same thing.
Our cells normally have DNA genomes, which make copies of the DNA genomes when they divide.
Are there different varieties of virus genomes?
Viruses can have all sorts of different genomes: double-stranded, single-stranded DNA, single-stranded or double-stranded RNA genome—it just depends on the virus.
DNA and RNA have slightly different chemistry and the proteins that make them are slightly different. That has some implications for the mutation rates and for the kind of molecule that the viruses must encode to be able to survive.
If viruses have double-stranded DNA genomes, they kind of work the same way as DNA does normally in us, and they can use all the enzymes of the cell they have invaded.
But if they have an RNA genome like SARS, they need a special enzyme that will make a copy of the RNA, called RdRp.
And how do mutations happen? Are they different in DNA vs. RNA viruses?
There's a complementarity between As and Ts, and Cs and Gs. Basically, you have one strand of either DNA or RNA and there's an enzyme that facilitates the binding of the complementary base of As and Ts, and Cs and Gs. One base will pair and bind with the other base.
For instance, an A should pair with a T or U, depending if it's DNA or RNA. But sometimes mutations occur if a wrong pairing happens. If A by mistake ends up pairing with, say, C, then that will be a mutation, because it will change the coding.“Mutations can do nothing, they can impair the virus, or they can facilitate the virus replication,” says Marta Gaglia. “If the virus transmits better, then it will more likely be selected [through evolution] to be dominant. If the virus transmits at the same rate, it’ll still transmit, but if it’s worse at transmitting, it’ll get lost.” Credit: Alonso Nichols
Our DNA-synthesizing machinery tends to have an error correction mechanism. It will figure out if there's a problem, usually because the structure is kind of weird if it's not the right pairing, it will excise and repair the mistake. That happens during replication. It's as if, while you were copying down a text and made typos, you could proofread and fix them.
The RNA-synthesizing machinery that most RNA viruses use to copy their genome doesn't have this error correction mechanism. But coronaviruses have a special enzyme that allows them to do error correction, so they have a lower mutation rate than other RNA viruses. I don't think it works quite as well as the DNA mechanism, though.
There's this idea that because most RNA viruses cannot error correct, they make lots and lots of mistakes. That's not great for us, because it allows them to mutate rapidly and avoid the immune system. But if they make too many mistakes, it's not good for the virus either, because the viruses will just break down.
And when the replication does make a mistake and it's not caught by the error correction, will the resulting virus be more successful or less successful?
There are three possibilities—mutations can do nothing, they can impair the virus, or they can facilitate the virus replication. If the virus transmits better, then it will more likely be selected [through evolution] to be dominant. If the virus transmits at the same rate, it'll still transmit, but if it's worse at transmitting, it'll get lost.
We've seen in the pandemic that mutations have arisen and then they became really widespread and for almost all of the ones we hear about, it became clear that they have at least slightly better transmission. I don't think it even has to be dramatically better. It just has to have a slight advantage over the original virus.
What else affects mutations?
The other aspect is that a virus will make hundreds to thousands of copies of itself every time it is in a cell. The chances of getting a mutant is high just because there's so many replications happening.
Better transmission doesn't necessarily mean that it's more virulent, right? It's just better at replicating and getting into the other cells?
Yes, it just means that the initial step of getting into cells is better. The development of the disease—the pathogenesis—has to do with many other things beside the replication of the virus.
Do variants of original viruses mix with other variants to create all new virus variants?
Each virus genome is alone, but you can imagine situations where you could have two viruses co-infecting the same cell, and in those cases, they might be able to compensate for each other.
There's definitely evidence that some coronaviruses can recombine, too. It there are two genomes that infect the same cell—just like our genomes are combined during the division of the stem cells—they could recombine into a fully fixed genome as it comes out. Those events might be quite rare, but because the virus replicates in an exponential way, even a rare event has a certain probability of occurring.
Do vaccines for viruses need to be updated when variants arise? We get a new flu vaccine every year because it's a different strain of the flu. Is that true with all viruses?
Some people are trying to develop a universal influenza vaccine, to try to target the antibody generation toward a part of the molecule that cannot change without making the molecule not work anymore.
With the coronavirus, we're not that sophisticated. But I think the evidence is that the variants are not escaping the vaccine dramatically. Still, it's something that people have definitely worried about and it's possible that we might have to update vaccines.
And of course, that also depends how quickly we can get this vaccination round to complete—how many different variants are going to emerge by the time most people are vaccinated. But I don't think there's any evidence that it's going to be quite like the flu.
How are influenza viruses different from coronaviruses?
They are RNA viruses, but they don't have the "proofreading" ability that the coronavirus has, so they have a lot of mutations. They definitely seem to have adapted to really take advantage of rapid change influenza seems to have developed a lifecycle that's all about changing so much that you never build a complete resistance.
That's not true for all viruses, though. The coronavirus definitely is not going to be like that. But if it does become endemic and it circulates in the population all the time, then there is a chance that a slightly different virus might emerge and we may need a booster.
Another question is, as people become immune thanks to vaccinations, is that going to be a strong pressure on the virus? Variants may emerge because people are immune to the old virus. Again, that's much more likely with something like influenza that has a much higher mutation rate, than with the coronavirus.
Evolutionary pathways to and from multipartitism
The different genome architectures observed in extant viruses might be solutions found after major viral families formed. In general, viruses experience frequent deletion and recombination events during replication, and HGT is common. Actually, homologies that indicate an evolutionary relationship between viruses with different genetic architectures (mono, bi, or tripartite, in early cases) and belonging to separated taxonomical groups have been known for long. 38 Gene sharing is in all likelihood directly involved in the plasticity observed in viruses at different taxonomic levels. The eventual success of a viral genome structure and architecture results from a highly contingent process. Nevertheless, viral host range does not seem to be conditioned by genome architecture: with the exception of dsDNA viruses, plants are infected by all types of genomes. There are examples of generalists such as the tripartite Cucumber mosaic virus (which infects over 1000 different plant hosts, both mono- and dicotyledons) or the tripartite Tomato spotted wilt tospovirus that infects 360 species from 50 families. However, uniform habitats and vegetative propagation may limit fitness optimization in generalists. Strains of Bean yellow mosaic virus have a limited range to local cultures of domesticated plants and Citrus tristeza virus infections are restricted to a few genera in the Rutaceae. 39,40,41 Anyhow, most plant viruses are generalists, and less than 10% of plant viruses infect one single host species. 42 As many as three to four different classes of viruses are often detected in an infected plant, 17,43 giving plenty of opportunities to explore the joint action of different viral genomes. This behavior could explain in part why multipartitism might have appeared repeatedly in the evolution of plant viruses. Still, possible evolutionary pathways and the specific advantage of multipartitism remain as open questions. In this section we present some ideas in this respect, following the hypothetical pathways depicted in Fig. 3. Evidence to support one or another evolutionary pathway is at present uneven.
Evolutionary pathways between genomic architectures. Here we represent some possible evolutionary routes relating viruses with non-segmented, segmented and multipartite genomes. Blue arrows correspond to processes that apply to all viruses regardless the capsid type orange and green arrows correspond to processes that apply to viruses with icosahedral and filamentous/rod-like capsids, respectively. This coarse-grained representation is further discussed in the main text, together with current empirical evidence, if any, and theoretical scenarios supporting the different pathways
Transitions from non-segmented to multipartite genomes
Defective particles are routinely generated upon replication of viral genomes. 44 Mutants with changes that preclude their viability in isolation and deletion mutants that lack genes essential to complete the viral cycle can however survive if complemented by viable genomes. Indeed, under conditions of high MOI, defective genomes thrive thanks to the activity in trans of products from viable genomes. In an infection cycle, segmentation might happen through additional mechanisms. Many RNA viruses regulate gene expression through subgenomic RNAs (sgRNA). Encapsidation of sgRNA with loose or non-existent sequence signals is possible. 45,46 However, as defective genomes, sgRNA particles are frequently lost in presence of the wild type.
There are some in vitro examples of a transition from an originally non-segmented virus to a bipartite one, 47 and some cases where genetic engineering techniques produced similar outcomes. 48,49 These facts suggested that an evolutionary transition from a non-segmented virus to a bipartite form should be possible, given an appropriate environment. An experimental demonstration of this possibility was realized with Foot-and-mouth disease virus (FMDV), an animal virus that was subjected to over 200 cell culture passages at a high MOI. 50 The bipartite, in vitro generated form that spontaneously appeared through evolution of the virus, displaced the wild type in competition under the experimental conditions. Subsequent experiments demonstrated that the superiority of the bipartite form was due to an increased stability of the viral capsid, which translated into an increased particle lifespan. 51 Finally, when the conditions of propagation were changed to low MOI, the two defective genomes recombined to produce a non-segmented form. 51 This experiment represents a proof-of-concept that a transition to bipartitism may occur as a result of a change in the ecological context (from low to high MOI in that case).
There is some recent evidence that genome segmentation might be a rare though possible route to multipartitism in virus. This has been suggested for genus Jingmenvirus for which evolutionary relationships with Flavivirus genus (non-segmented) have been established at least for two out of the four segments of the virus—the two other segments are of unknown origin. Flaviviruses infect various arthropods and vertebrates, and are arthropod-borne. Two Jingmenvirus species were described: Jingmen tick virus in ticks, mosquitoes, cattle 52 and red colobus monkey, 27 and Guaico culex virus in mosquitoes. 27 A transition to multipartitism plus a new association to other functional genes could have acted synergistically in the origin of Jingmenvirus.
Relationship between non-segmented, segmented, and multipartite viral genomes
It could be hypothesized that segmented viruses represent an intermediate state between non-segmented and multipartite genomes, at least for icosahedral viruses (Fig. 3). The rationale behind this possibility relies on the principle of parsimony: a complete genome could break into pieces due to replication errors and those segments could first encapsidate jointly—as it may have happened in the order Mononegavirales which comprises non-segmented and segmented viral families. This situation might favor the subsequent specialization of the segments, deleting overlapping regions and streamlining segment organization. In the final state the segments would be encapsidated in independent viral particles, as may be the case for the family Partitiviridae, which lacks encapsidation signals for the segments. Alternatively, filamentous viruses could have their origin in nucleocapsidic particles formerly enclosed in a complex capsid that at some point released them. Tenuiviruses may have originated through the latter pathway, given the high resemblances with Phlebovirus nucleocapsids. 53 These similarities between nucleocapsids of segmented Phleboviruses and filamentous capsids are also found in families Closteroviridae and Potyviridae, 54 which only contain bipartite species. This transition appears as a very plausible way for a recent origin of multipartitism. It may be aided in cases where different or smaller capsids could be horizontally acquired. Furthermore, a new capsid and, in general, the incorporation of novel segments, might grant access to a new collection of possible hosts, with the concomitant increase in the viral population size.
The intermediate segmented state of the former transition might be avoided by viruses with filamentous capsids (Fig. 3), representing an additional example of the transition from non-segmented to multipartite viruses described for Jingmenvirus in the previous section. The origin of filamentous families like Benyviridae and Virgaviridae may include the acquisition of TMV-like capsids in order to infect plants. 54 Co-encapsidation of segments generated due to replication errors or of sgRNAs is no longer possible, so multipartite encapsidation becomes unavoidable. Alternatively, enveloped animal viruses, with genomes wrapped in nucleocapsids, could be another source for filamentous multipartite viruses. 54 An example might be Rhabdoviridae, a family of enveloped viruses infecting invertebrates including bipartite genera infecting plants. The transmission from invertebrates to plants, and therefore the adaptation to a new ecological context, might have been concomitant with multipartition. 53
Reversibility through cooperation of the segments, and genome recombination, is likely a main force to revert to a non-segmented state (Fig. 3). In support of this statement comes the observation that non-segmented species are also found in families containing bi or tripartite viral genera, at odds to what is observed in segmented viral families, which do not simultaneously contain non-segmented or multipartite species.
Replication errors and the high numbers of viable and defective genomes simultaneously found within cells might enable mechanisms analogous to gene duplication and subfunctionalization 55 in viral genomes. Complementation in trans opens the door to the incorporation of new mutations in defective genomes without losing fitness and to, eventually, find new functions. Defective viral genomes can coexist for long in persistent infections, for instance evolving to truly hyper-parasitic forms and eventually causing the extinction of the viral population. 56 The persistence of defective segments is strongly linked to the frequency of population bottlenecks, 57 and their presence is rarely observed in vivo. However, it is not unthinkable that the once defective genome might change the overall properties of the initial wild type, allow adaptation to a new ecological niche, and eventually turn out to be essential for the survival of the new, bipartite virus.
Though recent gene duplications in RNA viruses are not abundant, there is evidence of one such event in Benyviridae, a multipartite family. 58 It cannot be discarded that many duplications are masked due to the rapid evolution of RNA viruses, and that remote paralogs can only be identified through the combined use of non-conventional techniques and manual curation. 59
Gene duplications are far more frequent in viruses with DNA genomes. 60 In Begomoviruses, 28,61 homologies between genes in the same segment have been identified, speaking for duplication events. A mechanism of the kind might have acted to cause the large number of segments of Nanoviruses: some of the parts of this viral family are dispensable in vitro. 29 Also, there is a significant degree of homology detected between some Nanovirus segments corresponding to regulatory sequences. 62 Another evidence for the rapid evolution of DNA multipartitism is recombination: 63 the incorporation of key regulatory sequences that control the addition of foreign genes in Begomoviruses might be instrumental to permit the independent replication of the segments in a short time, 64 and consequently the expansion to novel ecological niches. 65
De novo associations to multipartition
There are many instances in the Virosphere of transient associations of viruses with kin or with subviral agents 17 that often modify the aetiology of infections. A prominent example are the so-called viral satellites that is, subviral agents that require the assistance of a specific helper virus for its replication or encapsidation. 66 These associations are ubiquitous in plant infections, and less frequent in animal viruses—with some notable exceptions such as Hepatitis δ virus (HDV) 67 and the genus Dependoparvovirus, in the Parvoviridae family. 68 A sophisticated kind of satellite-like organism are virophages, which inhibit the replication of their host virus and are typically associated to giant viruses in the Mimiviridae family. 69 Another interesting class of hyper-parasites are viroid-like satellites consisting on a circular ssRNA dependent on plant viruses for replication and encapsidation, and not coding for any protein. The latter class and HDV are likely related to viroids, 70 non-coding circular RNAs which have been exclusively described infecting plants. 71 Some virus-satellite associations 72 are closely linked to the presence of multipartite genomes. Geminiviridae is the family of plant viruses with the largest number of examples: actually, this family contains many bipartite species but also a large number of species formed by non-segmented viruses that modify their virulence through the action of a satellite. 63 Additional examples are satellite Tobacco mosaic virus, which worsens the symptoms of the helper virus, 73 or the generalist CMV, whose association with a fourth non-essential satellite component modifies its virulence depending on the specific satellite 74 or on the infected host. 75
Cooperative interactions in mixed infections are also usual for RNA plant viruses. Co-infection of Potyviruses with other species of different families is also related with changes in the aetiology of the infection. Cooperation ultimately leads to interdependence (symbiosis) of two species belonging to different families, as it has been documented for Luteoviruses and Umbraviruses in Groundnut rosette virus or Pea enation mosaic virus. Long-term interactions may end up in speciation, and modular evolution of plant viruses could emerge as a consequence of independent evolutionary histories for individual genes within a genome. 43
Editorial: A home for virology, ecology, epidemiology, and evolutionary biology
1 Instituto de Biolog Molecular y Celular de Plantas, CSIC-UPV, València, Spain, 2 The Santa Fe Institute, Santa Fe, New Mexico, USA and 3 Department of Zoology, University of Oxford, UK
Oliver G. Pybus
1 Instituto de Biolog Molecular y Celular de Plantas, CSIC-UPV, València, Spain, 2 The Santa Fe Institute, Santa Fe, New Mexico, USA and 3 Department of Zoology, University of Oxford, UK
Viruses make headline news on an almost daily basis. Sometimes the news is positive, a report on the development of new anti-viral drugs or a reduction in transmission, perhaps. However, often the story will relate to a gloomier theme, for example, the appearance of new viral epidemics, the evolution of drug resistance, or falling vaccine coverage. The appearance of Ebola virus in West Africa since 2014 represents just the latest of a long series of devastating viruses that have emerged or expanded in humans in recent years, including Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) coronaviruses, Chikungunya virus, highly pathogenic avian influenza viruses, West Nile virus, and various human enteroviruses, and bunyaviruses. This list is both selective and anthropocentric and excludes numerous new epidemics in livestock (e.g., Schmallenberg virus), crop (e.g., tomato torrado virus), and wild animal populations (e.g., phocine distemper virus). The impacts of viral epidemics may extend beyond death and illness to cause substantial economic losses and social instability. Such effects are not limited to new or exotic viruses, as established and well-characterized viral diseases persist despite tremendous efforts to control and eradicate them. Important pathogens in this category include HIV/AIDS, human influenza viruses, dengue viruses, hepatitis viruses, human papillomaviruses, and rabies virus.
One reason that viruses are such potent adversaries is their great potential for genetic diversity and evolvability, a characteristic that they owe to a combination of short generation times, very large population sizes, and (in some but not all instances) error-prone replication mechanisms. Strains that escape host immune responses, are resistant to antiviral drugs, or, in the case of plant viruses, that break transgenic or natural genetic resistance, may arise in a viral population soon after it is challenged by the corresponding antiviral measure. Together, the outlook is mixed: the perspectives for future eradication or control are balanced by the emergence or re-emergence of new foes.
Although genetic diversity is an essential part of virus biology, classical approaches to virus control often ignore evolutionary processes and focus on understanding in great detail the molecular bases of pathogenesis, virus–host interaction, and drug–virus interference. This is despite the fact that evolutionary concepts are key to the correct interpretation of molecular variation among virus strains. Some experimental biologists, on the other hand, have taken advantage of the rapid evolution of many viruses and chosen to use them as model organisms for the investigation of fundamental questions in evolutionary biology (e.g., Elena and Sanjuán 2007). Moreover, in recent years, virus epidemiologists have begun to exploit the increasing availability of virus genome sequences and incorporated evolutionary thinking in their approach, leading to new insights into the ecological origins and transmission of viruses (e.g., Holmes 2009 Pybus and Rambaut 2009). Lastly, computational and theoretical biologists are developing increasingly complex models of virus behavior across all biological scales, from the cellular to the global, many of which attempt to explicitly represent the generation and dynamics of viral genetic diversity under different conditions (e.g., Nowak and May 2000 Wilke 2003 Luksza and Lässig 2014). Unfortunately, it is rare for all these diverse approaches to be taken into account when new strategies for virus control are designed. Why? Perhaps, at least until recently, there was insufficient exchange of ideas and concepts among these disciplines.
The study of virus evolution in its own right has flourished in the last 25 years and the subject undoubtedly gained greater recognition within the biological sciences after the discovery that evolution is an essential component of HIV infection. Since then, the number of published articles that use the term ‘virus evolution’ in the article title or summary has grown exponentially and doubled every 6𠄷 years ( Fig. 1 a). An equally striking pattern is seen if we plot occurrence of the same term in books written in English ( Fig. 1 b). The rate of growth of scientific papers that include ‘virus evolution’ is nearly twice that of those that mention only ‘virus’ ( Fig. 1 a) and approximately three times faster than the growth rate of PubMed as a whole (Lu 2011).
(a) Number of scientific articles using the terms ‘virus evolution’ or ‘virus’ in Thomson Reuters Web of Science between 1980 and 2015. Solid line: topic = (virus evolution) OR title = (virus evolution). Dashed line: topic = (virus) OR title = (virus), subtracting the numbers shown in the solid line. (b) Relative frequency of the term ‘virus evolution’ in the corpus of books published in English between 1940 and 2008. Data from Google’s Ngram Viewer (https://books.google.com/ngrams).
Where do all these manuscripts get published? Despite an explosion in virus evolution research activity, publications on the topic are scattered among a large number of journals that belong to a variety of categories from the Institute of Scientific Information (ISI). Although many studies appear in evolutionary biology journals, particularly those on viral experimental evolution, mathematical modeling, molecular evolution, and phylogenetics, a large proportion are submitted to journals that focus on virology and pathogenesis. In these disciplines, some editors express a preference for ‘mechanistic’ studies within a clear hypothetico-deductive framework and may not appreciate the importance of inferential and observational work within population and evolutionary biology. Further, several virology journals focus on either animal and plant viruses, so that relevant articles may not come to the attention of researchers from the other field. Viruses of bacteria, archaea, fungi, and protists are served comparatively poorly by the current literature, yet these groups are very likely to comprise the majority of viral genetic diversity on Earth. To add further fragmentation, some important theoretical work on virus variability and evolution is published in specialized mathematical journals that will not be well known to laboratory and field researchers.
We believe that the study of virus evolution would benefit from a common forum in which findings and ideas can be shared. We have established the journal Virus Evolution with this aim in mind, and we hope that it will grow into a successful and dynamic inter-disciplinary community of researchers interested in understanding why and how viruses have and continue to evolve. We aim to cover all aspects of virus evolution, ecology, and diversity with no restriction on host range or research methodology. To achieve this goal, we have assembled an Editorial Board whose members have made many important contributions to the field. The Board has expertise in animal, plant, and bacterial viruses and in a wide range of techniques, including experimental evolutionary biology, molecular epidemiology, metagenomics, structural biology, population genetics, ecology, and molecular virology. One benefit of a focused journal, such as Virus Evolution, is that the Editorial Board shares with the authorship a passion for the subject.
Our editorial philosophy is that Virus Evolution exists first and foremost to serve its authors and readers. To make publication in the journal a more pleasant experience, we impose no specific formatting requirements at submission: the manuscript can be provided in any style so long as it is readable by reviewers. Standard formatting will be requested only ter’ a paper has been accepted, at which point it should seem less of a chore. We will operate a traditional peer-review process but one that will emphasize the quality of reviews as well as their speed. Published papers will be available to read by all under an Open Access model that is compliant with all major funding bodies including the USA National Institutes of Health and UK Wellcome Trust. Lastly, accepted manuscripts will be visible online in the shortest possible time after acceptance.
We very much look forward to receiving your submissions and to begin working with the community to make Virus Evolution a vibrant and successful home for your research.
The exact evolutionary advantage of the polygenicity and polymorphism within the NKR cluster has remained puzzling. As the detection of “missing-self” can be achieved by monomorphic and conserved receptor ligand-interactions, the evolution of polymorphic iNKR genes seems redundant. Even more intriguing is the unknown role of aNKRs, for which most of the ligands have not been identified yet. In this work, we study the evolution of NKRs in host populations infected with different viral species. We find that viruses have a large evolutionary advantage when they evolve MHC-like molecules, especially if they are capable of downregulating the expression of MHC-I on infected hosts. In turn, hosts evolve expanded haplotypes composed of various specific aNKRs, and iNKRs that are specialized on particular MHC molecules. Thus, a polygenic and polymorphic NKR cluster encoding for specific receptors is beneficial to cope with coevolving pathogens.
To model this highly complex evolutionary process, simplifying assumptions were necessary. As discussed in detail in ( Carrillo-Bustamante et al. 2013, 2014), our ABM is inspired by humans and KIRs, which has the advantage of having realistic parameters for processes such as birth and death. However, by changing parameters, the ABM can be adapted to other species, as it qualitatively represents a model of the evolution of the expansion of the NKR complex. Indeed, our results hold true for different parameter settings and most of our assumptions (see Materials and Methods and Supplementary Data , Supplementary Data online). We have focused on modeling only the evolution of NKRs, while fixing MHC polymorphism, despite the fact that these systems coevolve ( Sambrook et al. 2005 Parham and Moffett 2013). Given that MHC-I alleles are evolutionary older than both Ly49 and KIR alleles, we chose to model the expansion and contraction of NKRs within an already existing MHC polymorphism. This choice has also practical reasons, as it is difficult to keep MHC polymorphism without including T-cell responses ( Borghans et al. 2004). We speculate that, if we were able to enable coevolution of MHC-I molecules, these would evolve some structure, enabling them to be recognized by the NKRs (e.g., similar to the HLA-A3/A11, Bw4, C1, and C2 epitopes that are known to be primary KIR ligands). The evolution of structured MHC-I ligands would in turn affect the evolution of NKR specificity and probably haplotype composition in a manner similar to what is reported here. Thus, we expect no large qualitative changes, as specificity (and hence diversity) remains necessary to successfully detect self from nonself.
Probably, the most critical assumption for our results is the asymmetry in the protection levels, as we assume that “at least one” aNKR, but “none” of the iNKRs should bind the viral molecule, to protect the host. We based this asymmetry on experimental data showing susceptibility and protection of mice to MCMV. C57BL/6 mice are resistant against MCMV because of their aNKR Ly49H binding the MCMV encoded protein m157 ( Arase et al. 2002 Smith et al. 2002), indicating that one aNKR directly recognizing decoy molecules is sufficient to provide protection. Similarly, the susceptibility of 129/J mice has been related to their iNKR Ly49I binding m157 with high affinity ( Smith et al. 2002). This observation suggests that the contribution of one single inhibiting receptor dominates, making the mice susceptible. The latter is surprising because those NK cell subsets that do not express iNKRs recognizing the decoy should be able to detect missing self, proliferate, and protect its host. Whether Ly49I is the only iNKR binding m157 remains unknown, but the data clearly demonstrate that one iNKR-m157 interaction is sufficient for the virus to evade immunosurveillance.
The spontaneous evolution of MHC-like molecules by both types of viruses in our model suggests that this evasion mechanism provides an evolutionary advantage for many viruses. A virus expressing MHC-mimics can avoid missing-self detection by engaging iNKRs, and will escape from aNKR-mediated NK cell responses as aNKRs should have low affinity for cognate MHC molecules. The few examples of CMV-encoded MHC-I-like molecules (including m157, and m04 in mice, and UL18 in humans) are in line with our findings. Given that MHC-like molecules evolve so easily in our model because of their evolutionary advantage, it remains intriguing why only few viral MHC mimics have been found in other viral species, but it is possible that these molecular mimics are encoded by short sequences, and are thereby difficult to identify. It has been suggested that NK cells play an important role during infection with persistent pathogens (such as CMV and other herpesviruses), as these viruses require constant vigilance ( Sun and Lanier 2009). Herpesviruses and poxviruses are large DNA viruses that employ many mechanisms to escape from the immune response. Several studies have successfully elucidated many of the immune evasion strategies used by EBV and CMV ( Hassink et al. 2005 van Gent, Braem, et al. 2014 van Gent, Gram, et al. 2014) by eliminating the expression of individual viral genes from infected cells and studying the effect of these viral mutants on the immune response. However, our current understanding of the immunoevasive mechanisms employed by these large DNA viruses is far from complete, and we would predict that these viruses encode more MHC-mimicking molecules than currently known. Extending this type of functional screening ( Hassink et al. 2005 van Gent, Braem, et al. 2014 van Gent, Gram, et al. 2014) to large number of viral proteins, and specifically assessing the effect of mutant viruses on NK cell responses, could confirm our predictions.
The characterization of specific ligands for aNKRs has remained difficult. Even though some specific interactions (e.g., Ly49H/m157, or Ly19P/m04-H2 k) have been identified, the ligands for most activating KIRs remain unknown. Our model shows that it is indeed difficult to evolve specific interactions between aNKRs and particular viral proteins as viruses evolve rapidly, and become a moving target for aNKRs, impeding the adaptation to particular infectious pathogens. Note that the specific interactions found in the mouse CMV model are from particular inbred mice strains infected with one specific laboratory CMV strain. In outbred wild mice, Ly49H-mediated resistance is rather uncommon ( Scalzo et al. 2005), confirming that there is large heterogeneity in the interactions between aNKRs and viruses.
Although iNKRs and aNKRs share a large sequence similarity in their extracellular binding domain, aNKRs do not bind the ligands of iNKRs ( Saulquin et al. 2003 Gillespie et al. 2007 O’Connor and McVicar 2013). Studies have even shown that there is an evolutionary trend in humans and chimpanzees toward reducing the affinity of the aNKRs to the HLA epitopes C1 and C2 ( Moesta et al. 2010). On the contrary, inhibitory KIRs have rather specific interactions, binding preferentially four epitopes on HLA molecules (A3/11, Bw4, C1 and C2) ( Moretta et al. 1996). We show that the specialization of iNKRs but not aNKRs on a small group of MHC-I molecules is advantageous to discriminate self/nonself more efficiently. However, the required specificity predicted by our model is higher than the known specificity for just four HLA-epitopes. Although binding experiments of KIR-Fc fusions to a broad panel of HLA molecules have revealed the specificity of KIR2DL2 and KIR2DL3 ( Moesta et al. 2008, 2010), an extension of these studies to a larger set of KIR alleles (including all inhibiting and activating KIRs) would reveal how many MHC-I molecules an NKR can recognize, and would establish the specificity of NKRs in a quantitative manner.
Summarizing, the evolution of both host receptors and viral immunomodulatory molecules is an ongoing dynamic process. We have shown that the NKR genetic complex evolves polygenicity and specificity in response to rapidly coevolving viruses.
Traditional 'cell-first' hypotheses
If, for a moment, we put aside the paradoxical virus-first hypothesis, we are left with two more traditional (cell-first) hypotheses about the origin of viruses in general. One is the 'escape hypothesis', which views viruses as originating from cells by the escape of a minimal set of cellular components necessary to constitute an infectious selfish replicating system. The other is the 'reduction hypothesis', in which viruses would have derived from a cellular organism through a progressive loss of functions until it finally became a bona fide virus. In real life, unfortunately, this simple dichotomy will be blurred by the accretion of genes laterally transferred between viruses (or parasitic cellular organisms) sharing identical hosts, or directly captured from the virus hosts. In that respect, bacteriophages differ markedly from most eukaryotic dsDNA viruses by exhibiting massive recombinational reassortment and accretion of genes, most probably resulting from the existence of a prophage state integrated into the host genome . Yet 80% of the genes of dsDNA bacteriophages have no obvious homologs in microbial genomes, suggesting a large degree of evolutionary independence of the phage gene set . A much stricter genetic isolation is exhibited by the eukaryotic nucleocytoplasmic large dsDNA viruses (NCLDV), such as the giant Acanthamoeba polyphaga mimivirus , whose 1.2 Mb genome (911 genes) exhibits little evidence of horizontal transfer . This also holds true for the next-largest NCLDVs, alga-infecting phycodnaviruses (with known genome sequences in the 300-400 kb range) [24, 25]. Mimivirus also exhibits a high level of genomic coherence, as shown by the homogeneity of its nucleotide composition and the strict conservation of half of its promoter sequences .
As more genomes of large eukaryotic viruses are sequenced, new genes keep turning up, most of them with no obvious phylogenetic affinity with known hosts or extant cellular organisms. This simple observation is definitely more favorable to the idea that these large viruses arose from the reduction of a more complex ancestral (viral) genome, than to the hypothetical accretion of numerous exogenous genes (without recognizable origin) around a primitive minimal viral genome. Recent results on coccolithovirus EhV-86 illustrate this point very nicely. Until the 407 kb genome of EhV-86 was characterized, the trademark of all previously characterized phycodnaviruses (with smaller 320 kb genomes) compared with other NCLDVs was the absence of a virus-encoded transcription machinery (a lack of DNA-directed RNA polymerase) . Obviously, the presence or absence of an RNA polymerase implies major differences in virus physiology. Unexpectedly, EhV-86 was found to encode its own six-subunit transcriptional machinery . Nevertheless, a phylogenetic analysis of 25 core genes common to NCLDVs firmly placed EhV-86 within the Phy-codnaviridae clade . In this case, the loss of the transcription apparatus by the smaller phycodnaviruses, rather than the simultaneous gain of the six subunits of an RNA polymerase by EhV-86, appears much more likely.
The reduction hypothesis received a strong boost from the discovery and genomic characterization of A. polyphaga mimivirus , the first virus to largely overlap with the world of cellular organisms, in terms of both particle size and genome complexity . The finding of numerous virally encoded components of an incomplete translation apparatus strongly suggested a process of reductive evolution from an even more complex ancestor that was endowed with protein synthetic capability. Such an ancestor could either have evolved from an obligate intracellular parasitic cell (functionally similar to Rickettsia or Chlamydia), or be derived from the nucleus of a primitive eukaryote through the mechanism illustrated in Figure 1. If reduction is the scenario at the origin of mimivirus, it is most likely to apply to other NCLDVs, in particular to those exhibiting the closest phylogenetic affinity with mimivirus such as the Phycodnaviridae and Iridoviridae. Sequencing additional large genomes from representatives of these families should provide valuable insights about this postulated giant ancestor.
The Important Role Played by Viruses in Human Evolution
Scientists have long pointed to the relationship between pathogens and evolution, but until very recently, they have been unable to pinpoint specific patterns which occur across different species. In a fascinating new study carried out by the Genetic Society of America, they have discovered (using big-data analysis) that viruses are responsible for an impressive 30 per cent of all protein adaptations since the human divergence with chimpanzees.
The study, published in the journal eLife and presented on 14 th July at The Allied Genetics Conference, showed that the adaptive patterns caused by viruses are strong and very clear. Never before have viruses been shown to have such a powerful effect on how human beings have adapted. The researchers found that adaptations occurred three times as frequently in proteins which interacted with viruses, as in other proteins.
Thanks to the study, scientists can now identify which parts of the cell have successfully defeated viruses in the past. The differences in protein shape and composition in response to these threats, could help scientists find new ways to battle the most powerful viral threats currently faced by human beings. Previous research had focused only on individual proteins which are directly involved in the immune response.
When the body is faced with a virus, proteins throughout the whole body react not only those involved with immunity. The researchers discovered that as much adaptation takes place outside the immune system, as within it. Viruses have affected us in every respect, affecting all parts of our cells. Proteins make a host of important cellular functions possible, so an analysis of tweaks and differences can give scientists vital clues as to how to face future threats. When pandemics and epidemics occur, populations must either adapt or risk becoming extinct and it is hoped that the observable changes in protein will help scientists new ways to help the body adapt.
The study helps scientists answer important questions, such as why species which are very similar have evolved different ways of fulfilling the same cellular function, such as cell membrane creation or DNA duplication. Scientists previously had no clue as to what evolutionary forces had provoked these similarities, and their results indicate that viruses hold vital secrets regarding the way different species have evolved.
The findings will have a great impact on the way researchers approach viral epidemics. Devastating viruses similar to HIV, for instance, have affected human beings and animals at many points in their long history. Seeing how cells have reacted to viruses of this type could help scientists glean a better understanding of how viruses work, and possibly lead to the discovery of how we can beat disease causing viruses for good, thus leading to greater health and a longer lifespan for humanity and other species.
Currently, viruses are taking countless lives, some of the most dangerous being the Marburg virus (which, like ebola, has a very high fatality rate), ebola (there are, thus far, five identified strains of the Ebola virus, which, like Marburg, has a fatality rate of 90 per cent), the Hantavirus (which actually comprises several types of virus and which can lead to lung disease, kidney failure and fever), some strains of bird flu, the Lass virus (whcich is transmitted by rodents), the Junin virus (which causes tissue inflammation), the Crima-Congo fever virus (transmitted by ticks and similar in its effects to Ebola and Margburg), the Machupo virus (which causes high fever and bleeding), the Kyasunur Forest Virus (which causes high fever, muscle pain and bleeding) and Dengue fever (passed on by a mosquito and boasting a very high fatality rate Dengue is common in popular tourist destinations such as Thailand, India and the Philippines, affecting between 50 and 100 million people a year).
Thus far, viruses are treated by addressing specific symptoms and complications. For instance, with Ebola, the key is to provide fluids and keep electrolyte levels stable, to maintain oxygen levels and blood pressure, and to treat any infections that arise. For other viruses, researchers are working to discover vaccines which will keep them at bay. What would give scientists the upper hand by mimicking protein adaptations, however, is the ability to actually manipulate cell function, instead of merely responding to symptoms.