Classification and nomenclature of endogenous retroviral sequences (ERVs)

Endogenous retroviruses (ERVs) differ from typical retroviruses in being inherited through the host germline and therefore are a unique combination of pathogen and selfish genetic element. Some ERV lineages proliferate by infecting germline cells, as do typical retroviruses, whereas others lack the env gene required for virions to enter cells and thus behave like retrotransposons. We wished to know what factors determined the relative abundance of different ERV lineages, so we analyzed ERV loci recovered from 38 mammal genomes by in silico screening. By modeling the relationship between proliferation and replication mechanism in detail within one group, the intracisternal A-type particles (IAPs), and performing simple correlations across all ERV lineages, we show that when ERVs lose the env gene their proliferation within that genome is boosted by a factor of ∼30. We also show that ERV abundance follows the Pareto principle or 20/80 rule, with ∼20% of lineages containing 80% of the loci. This rule is observed in many biological systems, including infectious disease epidemics, where commonly ∼20% of the infected individuals are responsible for 80% of onward infection. We thus borrow simple epidemiological and ecological models and show that retrotransposition and loss of env is the trait that leads endogenous retroviruses to becoming genomic superspreaders that take over a significant proportion of their host's genome. E ndogenous retroviruses (ERVs) proliferate by the repeated integration of new viral sequences into their host's germline (1), integrations which can become fixed in the host population and have led to ERV sequences (loci) comprising 8-10% of the human and mouse genomes (2, 3) (this number also includes nonautonomous LTR-retrotransposons, which we do not analyze here). These loci form phylogenetically distinct lineages traditionally called "families" (4) (unrelated to the general use of this term in taxonomy), each of which is the result of the expansion of a founder infection of the organism's germline that can have occurred more than ∼100 million years ago (5).ERVs can replicate both as transposable elements (TEs) and viruses. Some lineages copy by an entirely intracellular mechanism and are functionally indistinguishable from the class of TEs called LTR-retrotransposons, whereas others copy within the host germline using cell reinfection in the same manner as the copying within somatic cells of exogenous retroviruses (XRVs) (6). We refer to these replication mechanisms as "retrotransposition" and "reinfection," respectively. Whether an ERV is reinfecting or retrotransposing can be determined by the integrity of its env gene, which produces the protein on the surface of the viral particle that is responsible for cell entry. We can assume that an ERV lineage with a functional env is reinfecting, whereas an ERV lineage with a disintegrated env is retrotransposing (whether reinfection can include germline cells in other host individuals of the same or other species is not known). Some retroviruses w...

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“…ERVs are divided into three classes (22), and we find retrotransposing megafamilies in all of them (Fig. 1).…”

Section: Distribution Of Other Ervs In Hostsmentioning

confidence: 94%

Env-less endogenous retroviruses are genomic superspreaders

Magiorkinis

Gifford

Katzourakis

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

122

124

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“…Classifying and naming ERVs, particularly down to the level of individual proviral loci, remains a considerable problem (41,42), so far without final resolution. ERV sequences with internal homology to retroviruses can be placed into one of three classes based on phylogenetic analyses of the conserved regions of the pol gene.…”

Section: Structure and Classificationmentioning

confidence: 99%

Mammalian Endogenous Retroviruses

Mager

Stoye²

2015

Microbiol Spectr

171

103

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Over 40% of mammalian genomes comprise the products of reverse transcription. Among such retrotransposed sequences are those characterized by the presence of long terminal repeats (LTRs), including the endogenous retroviruses (ERVs), which are inherited genetic elements closely resembling the proviruses formed following exogenous retrovirus infection. Sequences derived from ERVs make up at least 8 to 10% of the human and mouse genomes and range from ancient sequences that predate mammalian divergence to elements that are currently still active. In this chapter we describe the discovery, classification and origins of ERVs in mammals and consider cellular mechanisms that have evolved to control their expression. We also discuss the negative effects of ERVs as agents of genetic disease and cancer and review examples of ERV protein domestication to serve host functions, as in placental development. Finally, we address growing evidence that the gene regulatory potential of ERV LTRs has been exploited multiple times during evolution to regulate genes and gene networks. Thus, although recently endogenized retroviral elements are often pathogenic, those that survive the forces of negative selection become neutral components of the host genome or can be harnessed to serve beneficial roles.

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“…5,9 HERVs can be classified into more than 20 families based on the transfer RNA specificity of the primer binding site used to initiate reverse transcription; thus, HERV-K would bind lysine and HERV-W, tryptophan, if they were replicating viruses. 10 HERVs have also been broadly grouped into three classes based on phylogenetic studies with exogenous retroviruses. 11 Class I HERVs are closer to gamma retroviruses, which include HERV-H and HERV-W; class II are closer to beta retroviruses and alpha retroviruses, and include HERV-K; class III are closer to spuma retroviruses, which include HERV-L and HERV-S. 11 Class I and class III HERVs are older and less evolved viruses, compared to class II HERV-K, which has the most complete sequence and, therefore, most likely to be biologically active in the human genome.…”

mentioning

confidence: 99%

K-type human endogenous retroviral elements in human melanoma

Rincon¹,

Sedrak²,

Sun³

et al. 2014

AGG

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Human endogenous retroviral elements (HERVs) are thought to be germline-integrated genetic remnants of exogenous retroviral infections. HERVs comprise approximately 5%-8% of the human genome. Although all HERV genomes are highly defective, some, especially the K type (HERV-K), have the potential to be expressed and have biological activities. HERV-K expression has been detected in human melanomas. There are also reports on the regulation and potential activities of HERV-K in melanoma cells. Although a causal link between the activation of HERV-K and melanoma development has yet to be determined, existing data support the further research efforts in this area. In this review, we summarize the published studies on the expression, regulation, and activity of HERV-K in human melanoma.

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Classification and nomenclature of endogenous retroviral sequences (ERVs)

Cited by 107 publications

References 70 publications

Env-less endogenous retroviruses are genomic superspreaders

Env-less endogenous retroviruses are genomic superspreaders

Mammalian Endogenous Retroviruses

K-type human endogenous retroviral elements in human melanoma

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