Trans-activation, post-transcriptional maturation, and induction of antibodies to HERV-K (HML-2) envelope transmembrane protein in HIV-1 infection

Henri Alexandre Michaud, Miguel de Mulder, Devi SenGupta, Steven G. Deeks, Jeffrey N. Martin, Christopher D. Pilcher, Frederick M. Hecht, Jonah B. Sacha, Douglas F. Nixon

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Article number10
JournalRetrovirology
Volume11
Issue number1
DOIs
StatePublished - Jan 28 2014

Keywords

  • Alternative transcripts
  • Antibody
  • Elite controllers
  • Endogenous retroviruses
  • Envelope
  • HERV
  • HIV
  • Transmembrane

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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    Michaud, H. A., de Mulder, M., SenGupta, D., Deeks, S. G., Martin, J. N., Pilcher, C. D., Hecht, F. M., Sacha, J. B., & Nixon, D. F. (2014). Trans-activation, post-transcriptional maturation, and induction of antibodies to HERV-K (HML-2) envelope transmembrane protein in HIV-1 infection. Retrovirology, 11(1), [10]. https://doi.org/10.1186/1742-4690-11-10