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

Authors

Henri-Alexandre Michaud, University of California - San Francisco
Miguel de Mulder, University of California - San Francisco
Devi SenGupta, University of California - San Francisco
Steven G. Deeks, University of California - San Francisco
Jeffrey N. Martin, University of California - San FranciscoFollow
Christopher D. Pilcher, University of California - San Francisco
Frederick M. Hecht, University of California - San Francisco
Jonah B. Sacha, Oregon Health & Science University
Douglas F. Nixon, George Washington UniversityFollow

Document Type

Journal Article

Publication Date

1-2014

Journal

Retrovirology

Volume

Volume 11

Inclusive Pages

Article number 10

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.

Comments

Reproduced with permission of Retrovirology.

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.

APA Citation

Michaud, H., de Mulder, M., SenGupta, D., Deeks, S.G., Martin, J.N. et al. (2014). Trans-activation, post-transcriptional maturation, and induction of antibodies to HERV-K (HML-2) envelope transmembrane protein in HIV-1 infection. Retrovirology, 11:10.

Peer Reviewed

1

Open Access

1