Human Endogenous Retrovirus Expression Is Inversely Associated with Chronic Immune Activation in HIV-1 Infection

PLOS ONE, August 2012

22879884

Christopher E. Ormsby, Devi SenGupta, Ravi Tandon, Steven G. Deeks, Jeffrey N. Martin, R. Brad Jones, Mario A. Ostrowski, Keith E. Garrison, Joel A. Vázquez-Pérez, Gustavo Reyes-Terán, Douglas F. Nixon

Human endogenous retroviruses (HERV) are remnants of ancestral retroviral infections integrated into the germ line, and constitute approximately 8% of the genome. Several autoimmune disorders, malignancies, and infectious diseases such as HIV-1 are associated with higher HERV expression. The degree to which HERV expression in vivo results in persistent inflammation is not known. We studied the association of immune activation and HERV-K expression in 20 subjects with chronic, untreated progressive HIV-1 infection and 10 HIV-1 negative controls. The mean HERV-K gag and env RNA expression level in the HIV-1 infected cohort was higher than in the control group (p = 0.0003), and was negatively correlated with the frequency of activated CD38+HLA-DR+CD4+ T cells (Rho = -0.61; p = 0.01) and activated CD38+HLA-DR+CD8+ T cells (Rho = -0.51; p = 0.03). Although HIV-infected persons had higher levels of HERV-K RNA expression (as expected), the level of RNA expression was negatively associated with level of T cell activation. The mechanism for this unexpected association remains to be defined.