Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Haitao Hu1,*,
  2. Martin Nau1,
  3. Phil Ehrenberg1,
  4. Agnes-Laurence Chenine1,
  5. Camila Macedo1,
  6. Yu Zhou2,
  7. Z. John Daye3,
  8. Zhi Wei4,
  9. Maryanne Vahey1,
  10. Nelson L Michael1,
  11. Jerome H Kim1,
  12. Mary Marovich1, and
  13. Silvia Ratto-Kim1
  1. 1 US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States;
  2. 2 Department of Pathology and Laboratory Medicine, Temple University, Philadelphia, PA, United States;
  3. 3 Division of Epidemiology and Biostatistics, University of Arizona Mel and Enid Zuckerman College of Public Health, Tucson, AZ, United States;
  4. 4 Department of Computer Science, New Jersey Institute of Technology, Newark, NJ, United States
  1. * Corresponding author; email: hhu{at}


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.