@article{e9b2adb5d7df447cab7d8f7570294e31,
title = "Trans-activation, post-transcriptional maturation, and induction of antibodies to HERV-K (HML-2) envelope transmembrane protein in HIV-1 infection",
abstract = "Background: Human Endogenous Retroviruses (HERVs) comprise about 8% of the human genome and have lost their ability to replicate or to produce infectious particles after having accumulated mutations over time. We assessed the kinetics of expression of HERV-K (HML-2) Envelope mRNA transcript and surface unit (SU) and transmembrane (TM) subunit proteins during HIV-1 infection. We also mapped the specificity of the humoral response to HERV-K (HML-2) Envelope protein in HIV-1 infected subjects at different stages of disease, and correlated the response with plasma viral load.Results: We found that HIV-1 modified HERV-K (HML-2) Env mRNA expression, resulting in the expression of a fully N-glycosylated HERV-K (HML-2) envelope protein on the cell surface. Serological mapping of HERV-K (HML-2) envelope protein linear epitopes revealed two major immunogenic domains, one on SU and another on the ectodomain of TM. The titers of HERV-K (HML-2) TM antibodies were dramatically increased in HIV-1 infected subjects (p < 0.0001). HIV-1 infected adults who control HIV-1 in the absence of therapy ({"} elite{"} controllers) had a higher titer response against TM compared to antiretroviral-treated adults (p < 0.0001) and uninfected adults (p < 0.0001).Conclusions: These data collectively suggest that HIV-1 infection induces fully glycosylated HERV-K (HML-2) envelope TM protein to which antibodies are induced. These anti-HERV-K (HML-2) TM antibodies are a potential marker of HIV-1 infection, and are at higher titer in elite controllers. HERV-K (HML-2) envelope TM protein may be a new therapeutic target in HIV-1 infection.",
keywords = "Alternative transcripts, Antibody, Elite controllers, Endogenous retroviruses, Envelope, HERV, HIV, Transmembrane",
author = "Michaud, {Henri Alexandre} and {de Mulder}, Miguel and Devi SenGupta and Deeks, {Steven G.} and Martin, {Jeffrey N.} and Pilcher, {Christopher D.} and Hecht, {Frederick M.} and Sacha, {Jonah B.} and Nixon, {Douglas F.}",
note = "Funding Information: We thank Dennis Burton, Nancy L Haigwood, Pheroze Joshi, Neil Sheppard, James Kobie, Jeffrey Milush, Andre Raposo, R. Brad Jones and Mario Ostrowksi for helpful discussions, and Pandey Suchitra, Gerald Spotts and Lisa Loeb for help in providing clinical specimens and data. We gratefully acknowledge reagents supplied from the NIH AIDS Research and Reference Reagent Program. This work was supported in part by grant number 108248-51-RGRL from amfAR, The Foundation for AIDS Research, The Bill & Melinda Gates Foundation (BMGF:01434000363), the Peter and Shelagh Godsoe Family Foundation thorough the AIDS Research Institute at UCSF, Pfizer Inc. through a sponsored research agreement, and funds from the National Institutes of Health (AI076059 and AI084113). This research was supported in part by a grant from the National Institutes of Health, University of California, San Francisco-Gladstone Institute of Virology & Immunology Center for AIDS Research, P30-AI027763 and the District of Columbia Developmental Center for AIDS Research (P30AI087714). The Options study is funded in part by NIAID (P01 AI071713). The SCOPE cohort is SCOPE supported in part by the NIAID (RO1 AI087145, K24AI069994, U19AI0961090), the UCSF/Gladstone Institute of Virology & Immunology CFAR (grant number P30 AI027763), the UCSF Clinical and Translational Research Institute Clinical Research Center (UL1 RR024131), the Center for AIDS Prevention Studies (P30 MH62246), and the CFAR Network of Integrated Systems (R24 AI067039). This work was supported in part by NIH OD 011092. The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: 1) HeLa T4+ from Dr. Richard Axel [54]. 2) TZM-bl from Dr. John C. Kappes, Dr. Xiaoyun Wu and Tranzyme Inc [51,55-57]. 3) HIV-1LAI from Dr. Jean-Marie Bechet and Dr. Luc Montagnier [58,59].",
year = "2014",
month = jan,
day = "28",
doi = "10.1186/1742-4690-11-10",
language = "English (US)",
volume = "11",
journal = "Retrovirology",
issn = "1742-4690",
publisher = "BioMed Central",
number = "1",
}