Complex Evolutionary History of Primate LentiviralvprGenes

AbstractVpx and Vpr are homologous proteins encoded by the human and simian immunodeficiency viruses. Vpr is encoded by each of the five primate lentiviral groups, whereas Vpx is restricted to members of the HIV-2 group. A recent report has proposed that thevpxgene was probably acquired from an ancestral member of the SIVagm group by nonhomologous recombination. Here, we suggest that this transfer event was more likely to have occurred via homologous recombination within the 3′ region of another gene,vif.Furthermore, phylogenetic analysis strongly suggests that there have been at least two other horizontal transfer events involving these genes: the first between ancestral members of the HIV-1 and HIV-2 groups, and the second between viruses isolated from the vervet and tantalus subspecies of African green monkey (Cercopithecus aethiopsssp)

Human Endogenous Retrovirus HC2 Is a New Member of the S71 Retroviral Subgroup with a Full-LengthpolGene

AbstractWe have isolated and characterized a new human endogenous provirus, which is closely related to the human retrovirus S71, but unlike S71 has a full-lengthpolgene. Two degenerate oligonucleotide primers based on highly conserved motifs within the active sites of two retroviral proteins (the protease and reverse transcriptase) were designed and used for PCR. An amplified product of 847 bp in length, which showed significant homology to protease and reverse transcriptase of several retroviruses, was used for high stringency hybridization with a human genomic library. The MuLV-related endogenous retrovirus sequence, designated HC2, was isolated and completely sequenced. HC2 is a provirus with completegagandpolgenes and a 3′ LTR; the 5′ LTR andenvgene are missing. Thegagandpolgenes appear complete, since they contain sequences homologous to the matrix protein, capsid protein, and nucleocapsid protein of gag and to the protease, reverse transcriptase, tether, RNase H, and integrase of pol. Phylogenetic analysis suggests that although HC2 and S71 are MuLV-related retroviruses, their characters are quite distinct, being placed outside of a clade containing most of the previously characterized MuLV-related retroviruses such as GaLV, FeLV, BaEV, and SSV/SSAV

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

Characterisation of retroviruses in the horse genome and their transcriptional activity via transcriptome sequencing

The recently released draft horse genome is incompletely characterised in terms of its repetitive element profile. This paper presents characterisation of the endogenous retrovirus (ERVs) of the horse genome based on a data-mining strategy using murine leukaemia virus proteins as queries. 978 ERV gene sequences were identified. Sequences were identified from the gamma, epsilon and betaretrovirus genera. At least one full length gammaretroviral locus was identified, though the gammaretroviral sequences are very degenerate. Using these data the RNA expression of these ERVs were derived from RNA transcriptome data from a variety of equine tissues. Unlike the well studied human and murine ERVs there do not appear to be particular phylogenetic groups of equine ERVs that are more transcriptionally active. Using this novel approach provided a more technically feasible method to characterise ERV expression than previous studies

Temperature and population density influence SARS-CoV-2 transmission in the absence of nonpharmaceutical interventions

As COVID-19 continues to spread across the world, it is increasingly important to understand the factors that influence its transmission. Seasonal variation driven by responses to changing environment has been shown to affect the transmission intensity of several coronaviruses. However, the impact of the environment on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains largely unknown, and thus seasonal variation remains a source of uncertainty in forecasts of SARS-CoV-2 transmission. Here we address this issue by assessing the association of temperature, humidity, ultraviolet radiation, and population density with estimates of transmission rate (R). Using data from the United States, we explore correlates of transmission across US states using comparative regression and integrative epidemiological modeling. We find that policy intervention ("lockdown") and reductions in individuals' mobility are the major predictors of SARS-CoV-2 transmission rates, but, in their absence, lower temperatures and higher population densities are correlated with increased SARS-CoV-2 transmission. Our results show that summer weather cannot be considered a substitute for mitigation policies, but that lower autumn and winter temperatures may lead to an increase in transmission intensity in the absence of policy interventions or behavioral changes. We outline how this information may improve the forecasting of COVID-19, reveal its future seasonal dynamics, and inform intervention policies

Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1

SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts. © 2013 Fregoso et al

Endogenous Retroviruses and Human Evolution

Humans share about 99% of their genomic DNA with chimpanzees and bonobos; thus, the differences between these species are unlikely to be in gene content but could be caused by inherited changes in regulatory systems. Endogenous retroviruses (ERVs) comprise ∼ 5% of the human genome. The LTRs of ERVs contain many regulatory sequences, such as promoters, enhancers, polyadenylation signals and factor-binding sites. Thus, they can influence the expression of nearby human genes. All known human-specific LTRs belong to the HERV-K (human ERV) family, the most active family in the human genome. It is likely that some of these ERVs could have integrated into regulatory regions of the human genome, and therefore could have had an impact on the expression of adjacent genes, which have consequently contributed to human evolution. This review discusses possible functional consequences of ERV integration in active coding regions