Oral keratinocytes support non-replicative infection and transfer of harbored HIV-1 to permissive cells

• Main Authors: Giacaman Rodrigo A, Fasching Claudine E, Gebhard Kristin H, Asrani Anil C, Vacharaksa Anjalee, Janoff Edward N, Ross Karen F, Herzberg Mark C
• Format: Article
• Language: English
• Published: BMC 2008-07-01
• Series: Retrovirology
• Online Access: http://www.retrovirology.com/content/5/1/66

<p>Abstract</p> <p>Background</p> <p>Oral keratinocytes on the mucosal surface are frequently exposed to HIV-1 through contact with infected sexual partners or nursing mothers. To determine the plausibility that oral keratinocytes are primary targets of HIV-1, we tested the hypothesis that HIV-1 infects oral keratinocytes in a restricted manner.</p> <p>Results</p> <p>To study the fate of HIV-1, immortalized oral keratinocytes (OKF6/TERT-2; TERT-2 cells) were characterized for the fate of HIV-specific RNA and DNA. At 6 h post inoculation with X4 or R5-tropic HIV-1, HIV-1<it>gag </it>RNA was detected maximally within TERT-2 cells. Reverse transcriptase activity in TERT-2 cells was confirmed by VSV-G-mediated infection with HIV-NL4-3Δenv-EGFP. AZT inhibited EGFP expression in a dose-dependent manner, suggesting that viral replication can be supported if receptors are bypassed. Within 3 h post inoculation, integrated HIV-1 DNA was detected in TERT-2 cell nuclei and persisted after subculture. Multiply spliced and unspliced HIV-1 mRNAs were not detectable up to 72 h post inoculation, suggesting that HIV replication may abort and that infection is non-productive. Within 48 h post inoculation, however, virus harbored by CD4 negative TERT-2 cells <it>trans </it>infected co-cultured peripheral blood mononuclear cells (PBMCs) or MOLT4 cells (CD4+ CCR5+) by direct cell-to-cell transfer or by releasing low levels of infectious virions. Primary tonsil epithelial cells also <it>trans </it>infected HIV-1 to permissive cells in a donor-specific manner.</p> <p>Conclusion</p> <p>Oral keratinocytes appear, therefore, to support stable non-replicative integration, while harboring and transmitting infectious X4- or R5-tropic HIV-1 to permissive cells for up to 48 h.</p>