Cutting Edge: An Antibody Recognizing Ancestral Endogenous Virus Glycoproteins Mediates Antibody-Dependent Cellular Cytotoxicity on HIV-1–Infected Cells

Abstract

The failure of antiviral vaccines is often associated with rapid viral escape from specific immune responses. In the past, conserved epitope or algorithmic epitope selections, such as mosaic vaccines, have been designed to diversify immunity and to circumvent potential viral escape. An alternative approach is to identify conserved stable non–HIV-1 self-epitopes present exclusively in HIV-1–infected cells. We showed previously that human endogenous retroviral (HERV) mRNA transcripts and protein are found in cells of HIV-1–infected patients and that HERV-K (HML-2)–specific T cells can eliminate HIV-1–infected cells in vitro. In this article, we demonstrate that a human anti–HERV-K (HML-2) transmembrane protein Ab binds specifically to HIV-1–infected cells and eliminates them through an Ab-dependent cellular cytotoxicity mechanism in vitro. Thus, Abs directed against epitopes other than HIV-1 proteins may have a role in eliminating HIV-1–infected cells and could be targeted in novel vaccine approaches or immunotherapeutic modalities.

Anti-HERV-K (HML-2) capsid antibody responses in HIV elite controllers

“…We, and others, have previously shown that HERV-K (HML-2) can be reactivated in HIV infection [ 26 – 28 ]. The mechanisms leading to HERV-K (HML-2) expression are still being elucidated, but HIV Vif and Tat proteins have been implicated [ 27 , 29 ].…”

Immune alterations in acute bipolar depression

“…The mechanisms involved in the activation of endogenous retroviruses and their role in immune activation should be the subject of additional investigations. The development of interventions directed at the prevention of the activation of other endogenous retroviruses suggests that the characterization of endogenous retrovirus activation in bipolar depression may eventually lead to novel therapeutic interventions.…”

Personalized gene therapy locks out HIV, paving the way to control virus without antiretroviral drugs

“…Distinguishing differences in the surface phenotype of cells from elite controllers of HIV compared with 'non-controllers' may provide a window for how viral infection can be controlled naturally, which could be used to design more effective strategies. Nixon and coworkers identified ancestral endogenous retroviral proteins that have been measured on the surface of infected HIV cells within 'elite controllers', and an antigen-specific T-cell response by HEV-K (HML-2)-specific T cells triggered a CTL response, as well as antigen-specific antibody for mediating a humoral response against HIV-infected cells makes the human endogenous retrovirus a promising target to consider for immunotherapy [83].…”