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

Anjalee Vacharaksa, Anil C. Asrani, Kristin H. Gebhard, Claudine E. Fasching, Rodrigo A. Giacaman, Edward N. Janoff, Karen F. Ross, Mark C. Herzberg

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Background: 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. Results: 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-1gag 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 trans 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 trans infected HIV-1 to permissive cells in a donor-specific manner. Conclusion: 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.

Original languageEnglish (US)
Article number66
JournalRetrovirology
Volume5
DOIs
StatePublished - Jul 17 2008

Bibliographical note

Funding Information:
These studies were supported by NIH grants-in-aid DE015503 (to MCH), DE15506 (KFR), HD41361 (ENJ), DE72621 (ENJ), the Veterans Affairs Research Service, and the Mucosal and Vaccine Research Center. This manuscript has been submitted in partial fulfillment of the requirements for the PhD degree in oral biology by AV.

Fingerprint

Dive into the research topics of 'Oral keratinocytes support non-replicative infection and transfer of harbored HIV-1 to permissive cells'. Together they form a unique fingerprint.

Cite this