Novel Denisovan and Neanderthal Retroviruses

Following the recent availability of high-coverage genomes for Denisovan and Neanderthal hominids, we conducted a screen for endogenized retroviruses, identifying six novel, previously unreported HERV-K(HML2) elements (HERV-K is human endogenous retrovirus K). These elements are absent from the human genome (hg38) and appear to be unique to archaic hominids. These findings provide further evidence supporting the recent activity of the HERV-K(HML2) group, which has been implicated in human disease. They will also provide insights into the evolution of archaic hominids

The molecular epidemiology of HIV-1 in the Comunidad Valenciana (Spain): analysis of transmission clusters

HIV infections are still a very serious concern for public heath worldwide. We have applied molecular evolution methods to study the HIV-1 epidemics in the Comunidad Valenciana (CV, Spain) from a public health surveillance perspective. For this, we analysed 1804 HIV-1 sequences comprising protease and reverse transcriptase (PR/RT) coding regions, sampled between 2004 and 2014. These sequences were subtyped and subjected to phylogenetic analyses in order to detect transmission clusters. In addition, univariate and multinomial comparisons were performed to detect epidemiological differences between HIV-1 subtypes, and risk groups. The HIV epidemic in the CV is dominated by subtype B infections among local men who have sex with men (MSM). 270 transmission clusters were identified (>57% of the dataset), 12 of which included ≥10 patients; 11 of subtype B (9 affecting MSMs) and one (n = 21) of CRF14, affecting predominately intravenous drug users (IDUs). Dated phylogenies revealed these large clusters to have originated from the mid-80s to the early 00 s. Subtype B is more likely to form transmission clusters than non-B variants and MSMs to cluster than other risk groups. Multinomial analyses revealed an association between non-B variants, which are not established in the local population yet, and different foreign groups

Analysis of spounaviruses as a case study for the overdue reclassification of tailed phages

Tailed bacteriophages are the most abundant and diverse viruses in the world, with genome sizes ranging from 10 kbp to over 500 kbp. Yet, due to historical reasons, all this diversity is confined to a single virus order-Caudovirales, composed of just four families: Myoviridae, Siphoviridae, Podoviridae, and the newly created Ackermannviridae family. In recent years, this morphology-based classification scheme has started to crumble under the constant flood of phage sequences, revealing that tailed phages are even more genetically diverse than once thought. This prompted us, the Bacterial and Archaeal Viruses Subcommittee of the International Committee on Taxonomy of Viruses (ICTV), to consider overall reorganization of phage taxonomy. In this study, we used a wide range of complementary methods-including comparative genomics, core genome analysis, and marker gene phylogenetics-to show that the group of Bacillus phage SPO1-related viruses previously classified into the Spounavirinae subfamily, is clearly distinct from other members of the family Myoviridae and its diversity deserves the rank of an autonomous family. Thus, we removed this group from the Myoviridae family and created the family Herelleviridae-a new taxon of the same rank. In the process of the taxon evaluation, we explored the feasibility of different demarcation criteria and critically evaluated the usefulness of our methods for phage classification. The convergence of results, drawing a consistent and comprehensive picture of a new family with associated subfamilies, regardless of method, demonstrates that the tools applied here are particularly useful in phage taxonomy. We are convinced that creation of this novel family is a crucial milestone toward much-needed reclassification in the Caudovirales order.Peer reviewe

Marine origin of retroviruses in the early Palaeozoic Era

Very little is known about the ancient origin of retroviruses, but owing to the discovery of their ancient endogenous viral counterparts, their early history is beginning to unfold. Here we report 36 lineages of basal amphibian and fish foamy-like endogenous retroviruses (FLERVs). Phylogenetic analyses reveal that ray-finned fish FLERVs exhibit an overall co-speciation pattern with their hosts, while amphibian FLERVs might not. We also observe several possible ancient viral cross-class transmissions, involving lobe-finned fish, shark and frog FLERVs. Sequence examination and analyses reveal two major lineages of ray-finned fish FLERVs, one of which had gained two novel accessory genes within their extraordinarily large genomes. Our phylogenetic analyses suggest that this major retroviral lineage, and therefore retroviruses as a whole, have an ancient marine origin and originated together with, if not before, their jawed vertebrate hosts >450 million years ago in the Ordovician period, early Palaeozoic Era

Marine origin of retroviruses in the early Palaeozoic Era

Very little is known about the ancient origin of retroviruses, but owing to the discovery of their ancient endogenous viral counterparts, their early history is beginning to unfold. Here we report 36 lineages of basal amphibian and fish foamy-like endogenous retroviruses (FLERVs). Phylogenetic analyses reveal that ray-finned fish FLERVs exhibit an overall co-speciation pattern with their hosts, while amphibian FLERVs might not. We also observe several possible ancient viral cross-class transmissions, involving lobe-finned fish, shark and frog FLERVs. Sequence examination and analyses reveal two major lineages of ray-finned fish FLERVs, one of which had gained two novel accessory genes within their extraordinarily large genomes. Our phylogenetic analyses suggest that this major retroviral lineage, and therefore retroviruses as a whole, have an ancient marine origin and originated together with, if not before, their jawed vertebrate hosts >450 million years ago in the Ordovician period, early Palaeozoic Era

The genomic underpinnings of eukaryotic virus taxonomy: creating a sequence-based framework for family-level virus classification

The International Committee on Taxonomy of Viruses (ICTV) classifies viruses into families, genera and species and provides a regulated system for their nomenclature that is universally used in virus descriptions. Virus taxonomic assignments have traditionally been based upon virus phenotypic properties such as host range, virion morphology and replication mechanisms, particularly at family level. However, gene sequence comparisons provide a clearer guide to their evolutionary relationships and provide the only information that may guide the incorporation of viruses detected in environmental (metagenomic) studies that lack any phenotypic data.The current study sought to determine whether the existing virus taxonomy could be reproduced by examination of genetic relationships through the extraction of protein-coding gene signatures and genome organisational features. We found large-scale consistency between genetic relationships and taxonomic assignments for viruses of all genome configurations and genome sizes. The analysis pipeline that we have called 'Genome Relationships Applied to Virus Taxonomy' (GRAViTy) was highly effective at reproducing the current assignments of viruses at family level as well as inter-family groupings into orders. Its ability to correctly differentiate assigned viruses from unassigned viruses, and classify them into the correct taxonomic group, was evaluated by threefold cross-validation technique. This predicted family membership of eukaryotic viruses with close to 100% accuracy and specificity potentially enabling the algorithm to predict assignments for the vast corpus of metagenomic sequences consistently with ICTV taxonomy rules. In an evaluation run of GRAViTy, over one half (460/921) of (near)-complete genome sequences from several large published metagenomic eukaryotic virus datasets were assigned to 127 novel family-level groupings. If corroborated by other analysis methods, these would potentially more than double the number of eukaryotic virus families in the ICTV taxonomy.A rapid and objective means to explore metagenomic viral diversity and make informed recommendations for their assignments at each taxonomic layer is essential. GRAViTy provides one means to make rule-based assignments at family and order levels in a manner that preserves the integrity and underlying organisational principles of the current ICTV taxonomy framework. Such methods are increasingly required as the vast virosphere is explored

Virus classification - where do you draw the line?

High-throughput sequencing (HTS) and its use in recovering and assembling novel virus sequences from environmental, human clinical, veterinary and plant samples has unearthed a vast new catalogue of viruses. Their classification, known by their sequences alone, sets a major challenge to traditional virus taxonomy, especially at the family and species levels, which have been historically based largely on descriptive taxon definitions. These typically entail some knowledge of their phenotypic properties, including replication strategies, virion structure and clinical and epidemiological features, such as host range, geographical distribution and disease outcomes. Little to no information on these attributes is available, however, for viruses identified in metagenomic datasets. If such viruses are to be included in virus taxonomy, their assignments will have to be guided largely or entirely by metrics of genetic relatedness. The immediate problem here is that the International Committee on Taxonomy of Viruses (ICTV), an organisation that authorises the taxonomic classification of viruses, provides little or no guidance on how similar or how divergent viruses must be in order to be considered members of new species or new families. We have recently developed a method for scoring genomic (dis)similarity between viruses (Genome Relationships Applied to Virus Taxonomy - GRAViTy) among the eukaryotic and prokaryotic viruses currently classified by the ICTV. At the family and genus levels, we found large-scale consistency between genetic relationships and their taxonomic assignments for eukaryotic viruses of all genome configurations and genome sizes. Family assignments of prokaryotic viruses have, however, been made at a quite different genetic level, and groupings currently classified as sub-families are a much better match to the eukaryotic virus family level. These findings support the ongoing reorganisation of bacteriophage taxonomy by the ICTV Phage Study Group. A rapid and objective means to explore metagenomic viral diversity and make evidence-based assignments for such viruses at each taxonomic layer is essential. Analysis of sequences by GRAViTy provides evidence that family (and genus) assignments of currently classified viruses are largely underpinned by genomic relatedness, and these features could serve as a guide towards an evidence-based classification of metagenomic viruses in the future

Prisoners of war — host adaptation and its constraints on virus evolution

Recent discoveries of contemporary genotypes of hepatitis B virus and parvovirus B19 in ancient human remains demonstrate that little genetic change has occurred in these viruses over 4,500–6,000 years. Endogenous viral elements in host genomes provide separate evidence that viruses similar to many major contemporary groups circulated 100 million years ago or earlier. In this Opinion article, we argue that the extraordinary conservation of virus genome sequences is best explained by a niche-filling model in which fitness optimization is rapidly achieved in their specific hosts. Whereas short-term substitution rates reflect the accumulation of tolerated sequence changes within adapted genomes, longer-term rates increasingly resemble those of their hosts as the evolving niche moulds and effectively imprisons the virus in co-adapted virus–host relationships. Contrastingly, viruses that jump hosts undergo strong and stringent adaptive selection as they maximize their fit to their new niche. This adaptive capability may paradoxically create evolutionary stasis in long-term host relationships. While viruses can evolve and adapt rapidly, their hosts may ultimately shape their longer-term evolution