title: HIV-1 infection leads to increased transcription of human endogenous retrovirus HERV-K (HML-2) proviruses in vivo but not to increased virion production.
abstract: Recent studies suggest that human endogenous retrovirus group K (HERV-K) provirus expression plays a role in the pathogenesis of HIV-1 infection. In particular, RNA from the HML-2 subgroup of HERV-K proviruses has been reported to be highly expressed at the cellular level and detectable in the plasma of HIV-1-infected patients, suggestive of virion production and, perhaps, replication. In this study, we developed an HML-2-specific quantitative-PCR assay that detects 51 of the 89 known HML-2 proviruses in the human genome. Plasma and peripheral blood mononuclear cells (PBMCs) from HIV-negative controls and HIV-1-infected patients were collected for analysis of HML-2 RNA expression. Contrary to previous reports, we did not detect high levels of HML-2 RNA in the plasma of HIV-1-infected patients, but we did observe a significant increase of HML-2 RNA in total PBMCs compared to HIV-negative controls. The level of HML-2 expression in PBMCs does not appear to be related to patient use of antiretrovirals or to HIV-1 plasma RNA, cellular RNA, or cellular DNA levels. To investigate the source of HML-2 RNA expression, patient PBMCs were sorted into CD3+ CD4+, CD3+ CD8+, CD3- CD14+, and CD3- CD20+ cell subsets and then analyzed for HML-2 RNA levels. No single cell subset was enriched for HML-2 RNA expression in HIV-1-infected patients, but there appears to be substantial variability in the level of HML-2 expression depending on the cell type.
  
  
  OBJECTIVE
  Here, we report that human endogenous retrovirus group K (HERV-K) (HML-2) proviruses are expressed at significantly higher levels in peripheral blood mononuclear cells (PBMCs) from patients with HIV-1 infection than in those from uninfected individuals. However, contrary to previous reports, this expression did not lead to detectable virions in the plasma of these patients. In addition, we found that HML-2 proviruses were expressed in multiple blood cell types from HIV-1-infected individuals, and the magnitude of HML-2 expression was not related to HIV-1 disease markers in this patient cohort. These findings may have implications for HML-2-based therapies targeting HIV-1 infection.
authors: Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, USA.
authors: Neeru
authors: N
authors: Bhardwaj
authors: HIV Drug Resistance Program, NCI Frederick, NIH, Frederick, Maryland, USA.
authors: Frank
authors: F
authors: Maldarelli
authors: Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: John
authors: J
authors: Mellors
authors: Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, USA john.coffin@tufts.edu.
authors: John M
authors: JM
authors: Coffin
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000276:immunology; D005260:Female; D015870:Gene Expression; D015894:Genome, Human; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011533:Proviruses / Q000235:genetics* / Q000276:immunology; D012367:RNA, Viral / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000821:virology; D014158:Transcription, Genetic; D014771:Virion / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D012367:RNA, Viral