Human endogenous retroviruses in health and disease: a symbiotic perspective

Ryan, Frank

doi:10.1258/jrsm.97.12.560

Cited by 80 publications

(47 citation statements)

References 39 publications

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“…HERVs represent about 8% of the human genome (Ryan, 2004). The analysis by Tristem (Tristem, 2000) confirms previous reports that the vast majority of HERV elements are defective by virtue of deletions or stop codons in gag, pol or env genes.…”

Section: Placental Endogenous Retroviral Envelope Proteinssupporting

confidence: 83%

“…Retroviruses can be defined as a class of enveloped viruses that have their genetic material in the form of RNA and use the enzyme reverse transcriptase to translate their RNA into DNA in a host cell (Ryan, 2004). All retroviruses contain information coding for three defined sets of regions of genes: gag (group specific antigen), pol (polymerase) and env (envelope).…”

Section: Placental Endogenous Retroviral Envelope Proteinsmentioning

confidence: 99%

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Mechanisms of Maternal Immune Tolerance During Pregnancy

Schjenken¹,

Tolosa²,

Paul³

et al. 2012

Recent Advances in Research on the Human Placenta

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Section: Placental Endogenous Retroviral Envelope Proteinssupporting

confidence: 83%

Section: Placental Endogenous Retroviral Envelope Proteinsmentioning

confidence: 99%

Mechanisms of Maternal Immune Tolerance During Pregnancy

Schjenken¹,

Tolosa²,

Paul³

et al. 2012

Recent Advances in Research on the Human Placenta

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“…Indeed, genome sequencing reveals that 8% of the human genome consists of human endogenous retroviruses (54,55). In this respect, it is interesting to consider that pandemic plagues are ultimately a brutal manifestation of an evolutionary mechanism resulting in changes to the species gene pool through a protracted series of invasions with repeated large-scale attrition and that the exogenous forebears of our human endogenous retroviruses once behaved as highly contagious infections, following transmission pathways akin to that of HIV-1 (56). HIV-1 has a highly diverse viral population both within an infected individual and across populations of hosts (57).…”

Section: Discussionmentioning

confidence: 99%

Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Matrix Proteins Specify Different Capabilities To Modulate B Cell Growth

Caccuri

Giagulli

Reichelt

et al. 2014

J Virol

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Exogenous HIV-1 matrix protein p17 (p17) deregulates the function of different cells after its N-terminal loop (AT20) binding to the chemokine receptors CXCR1 and CXCR2. One site within AT20 has been recently found to be the major determinant of viral fitness following transmission of simian immunodeficiency virus (SIV) to the human host. Therefore, we sought to determine whether SIV matrix protein (MA) was already capable of interacting with CXCR1 and CXCR2 and mimic p17 biological activities rather than this being a newly acquired function during host adaptation. We show here that SIV MA binds with the same affinity of p17 to CXCR1 and CXCR2 and displays both p17 proangiogenic on human primary endothelial cells and chemotactic activity on human primary monocytes and B cells. However, SIV MA exhibited a higher degree of plasticity than p17 in the C terminus, a region known to play a role in modulating B cell growth. Indeed, in contrast to p17, SIV MA was found to activate the phosphatidylinositol 3-kinase/Akt signaling pathway and strongly promote B cell proliferation and clonogenic activity. Interestingly, we have recently highlighted the existence of a Ugandan HIV-1 strain-derived p17 variant (S75X) with the same B cell growth-promoting activity of SIV MA. Computational modeling allowed us to hypothesize an altered C terminus/core region interaction behind SIV MA and S75X activity. Our findings suggest the appearance of a structural constraint in the p17 C terminus that controls B cell growth, which may help to elucidate the evolutionary trajectory of HIV-1. IMPORTANCEThe HIV-1 matrix protein p17 (p17) deregulates the biological activities of different cells after binding to the chemokine receptors CXCR1 and CXCR2. The p17 functional domain responsible for receptors interaction includes an amino acid which is considered the major determinant of SIV replication in humans. Therefore, we sought to determine whether SIV matrix protein (SIV MA) already had the ability to bind to both chemokine receptors rather than being a function newly acquired during host adaptation. We show here that SIV MA binds to CXCR1 and CXCR2 and fully mimics the p17 proangiogenic and chemokine activity. However, it differs from p17 in its ability to signal into B cells and promote B cell growth and clonogenicity. Computational analysis suggests that the accumulation of mutations in the C-terminal region may have led to a further SIV MA adaptation to the human host. This finding in turn sheds light on the evolutionary trajectory of HIV-1.

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“…There is growing evidence that retroviruses and endogenous retroviruses have played a major role in the evolution of animal and, most particularly, human adaptive immunity (56,57,63,65). Recently, nonretroviral integration-based immunity was proposed (5,15,36).…”

Section: Direction Of Hgtsmentioning

confidence: 99%

Widespread Horizontal Gene Transfer from Double-Stranded RNA Viruses to Eukaryotic Nuclear Genomes

Liu

Fù

Jiāng

et al. 2010

J Virol

207

161

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Horizontal gene transfer commonly occurs from cells to viruses but rarely occurs from viruses to their host cells, with the exception of retroviruses and some DNA viruses. However, extensive sequence similarity searches in public genome databases for various organisms showed that the capsid protein and RNA-dependent RNA polymerase genes from totiviruses and partitiviruses have widespread homologs in the nuclear genomes of eukaryotic organisms, including plants, arthropods, fungi, nematodes, and protozoa. PCR amplification and sequencing as well as comparative evidence of junction coverage between virus and host sequences support the conclusion that these viral homologs are real and occur in eukaryotic genomes. Sequence comparison and phylogenetic analysis suggest that these genes were likely transferred horizontally from viruses to eukaryotic genomes. Furthermore, we present evidence showing that some of the transferred genes are conserved and expressed in eukaryotic organisms and suggesting that these viral genes are also functional in the recipient genomes. Our findings imply that horizontal transfer of double-stranded RNA viral genes is widespread among eukaryotes and may give rise to functionally important new genes, thus entailing that RNA viruses may play significant roles in the evolution of eukaryotes.

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Human endogenous retroviruses in health and disease: a symbiotic perspective

Cited by 80 publications

References 39 publications

Mechanisms of Maternal Immune Tolerance During Pregnancy

Mechanisms of Maternal Immune Tolerance During Pregnancy

Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Matrix Proteins Specify Different Capabilities To Modulate B Cell Growth

Widespread Horizontal Gene Transfer from Double-Stranded RNA Viruses to Eukaryotic Nuclear Genomes

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