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

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• 作者：Henri-Alexandre Michaud (1)
  Miguel de Mulder (1)
  Devi SenGupta (1)
  Steven G Deeks (2)
  Jeffrey N Martin (3)
  Christopher D Pilcher (2)
  Frederick M Hecht (2)
  Jonah B Sacha (4) (5)
  Douglas F Nixon (1) (6)
  
• 关键词：HIV ; Antibody ; HERV ; Endogenous retroviruses ; Transmembrane ; Envelope ; Elite controllers ; Alternative transcripts
• 刊名：Retrovirology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：11
• 期：1
• 全文大小：998 KB
• 作者单位：Henri-Alexandre Michaud (1)
  Miguel de Mulder (1)
  Devi SenGupta (1)
  Steven G Deeks (2)
  Jeffrey N Martin (3)
  Christopher D Pilcher (2)
  Frederick M Hecht (2)
  Jonah B Sacha (4) (5)
  Douglas F Nixon (1) (6)
  
  1. Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, USA
  2. HIV/AIDS Program, Department of Medicine, University of California, San Francisco, USA
  3. Department of Epidemiology and Biostatistics, University of California, San Francisco, USA
  4. Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, 97006, USA
  5. Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, 97006, USA
  6. Microbiology, Immunology & Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Ross Hall 502, 2300 Eye Street, NW, Washington, DC, 20037, USA
  
• ISSN：1742-4690

文摘

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-lt;-.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-lt;-.0001) and uninfected adults (p-lt;-.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.