Distinct gene expression profiles associated with the susceptibility of pathogen-specific CD4 T cells to HIV-1 infection

Haitao Hu, Martin Nau, Phil Ehrenberg, Agnes-Laurence Chenine, Camila Macedo, Yu Zhou, Z. John Daye, Zhi Wei, Maryanne Vahey, Nelson L Michael, Jerome H Kim, Mary Marovich and Silvia Ratto-Kim


In HIV infection, the CD4 responses to opportunistic pathogens like Candida albicans are lost early, but cytomegalovirus (CMV)-specific CD4 response persists. Little is currently known about HIV infection of CD4 T cells of different pathogen/antigen specificity. CFSE-labeled PBMC were stimulated with CMV, Tetanus Toxoid (TT) and Candida antigens and subsequently exposed to HIV. HIV infection was monitored by intracellular p24 in CFSE-low population. We showed that while TT- and Candida-specific CD4 T cells were permissive, CMV-specific CD4 T cells were highly resistant to both R5 and X4 HIV. Quantification of HIV DNA in CFSE-low cells showed a reduction of strong-stop and full-length DNA in CMV-specific cells compared to TT- and Candida-specific cells. β-chemokine neutralization enhanced HIV entry and infection in TT- and Candida-specific cells, whereas HIV infection in CMV-specific cells remained low despite increased HIV entry by β-chemokine neutralization, suggesting post-entry restriction of HIV replication by CMV-specific cells. Microarray analysis (GEO Accession Number: GSE42853) revealed distinct transcriptional profiles that involved selective upregulation of comprehensive innate antiviral genes in CMV-specific cells, whereas TT- and Candida-specific cells mainly upregulated Th17 inflammatory response. Our data suggest a mechanism for persistence of CMV-specific CD4 response and earlier loss of mucosal Th17-associated TT- and Candida-specific CD4 response in AIDS.

  • Submitted July 27, 2012.
  • Accepted November 26, 2012.