Eight percent of the human genome is of retroviral origin. Human endogenous retroviruses (HERV-K) RNA, proteins and virions have been detected in patients with cancer and HIV-1. There is abundant evidence that the expression of many endogenous retroviruses is up-regulated upon HIV-1 infection. Thus, HIV-1 infection in human cells is equivalent to a co-infection of several retroviruses. Because of the negative selection HERVs are subjected to, most of those endogenous retroviruses have lost their ability to replicate. We hypothesize that the interactions between endogenous retroviruses and HIV affect the outcome of exogenous the lentivirus infection and replication. Although there are at least 89 HERV-Ks in the human genome often they are studied as single provirus. Our objective is to delineate the full array of HERV-K transcripts present in primary cells prior as well as after infection with HIV, and determine how these co-infections change cellular and viral properties such as target cell susceptibility, viral infectivity and cell tropism. We propose to combine state-of-the-art deep sequencing technologies with molecular virology approaches to study HIV/HERV-K interactions at the molecular level. This approach will deliver: HERV-K expression profiling in primary cells in both infect and non-infected settings as well as the establishment of the impact that the relevant HERV-Ks have on the early late stages of the HIV life cycle.

Public Health Relevance

This proposal describes sets of experiments aimed at testing the hypothesis that HIV-1 replication and pathogenesis are influenced by the expression of endogenous retroviruses. Eight percent of the human genome is of retroviral origin. Although most of the human endogenous retroviruses (HERVs) are inactivated, either structurally or transcriptionally HERV expression is reactivated by HIV infection. These studies will provide insight to the biological consequences of such HERV-K Env /HIV interaction which alongside the fundamental new knowledge regarding the nature of the HERV-K influence on HIV will set the basis for studies concerning new therapeutic approaches targeting HIV replication.

National Institute of Health (NIH)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Sakalian, Michael
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Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
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