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, Silvia Ratto-Kim

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

In HIV infection, CD4 responses to opportunistic pathogens such as Candida albicans are lost early, but CMV-specific CD4 response persists. Little is currently known about HIV infection of CD4 T cells of different pathogen/antigen specificities. CFSE-labeled PBMCs were stimulated with CMV, tetanus toxoid (TT), and C albicans antigens and subsequently exposed to HIV. HIV infection was monitored by intracellular p24 in CFSElow population. We found that although TT-and C albicans-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 CFSElow cells showed a reduction of strong-stop and full-length DNA in CMV-specific cells compared with TT-and C albicans-specific cells. β-Chemokine neutralization enhanced HIV infection in TT-and C albicans-specific cells, whereas HIV infection in CMV-specific cells remained low despite increased entry by β-chemokine neutralization, suggesting postentry HIV restriction by CMV-specific cells. Microarray analysis (Gene Expression Omnibus accession number: GSE42853) revealed distinct transcriptional profiles that involved selective up-regulation of comprehensive innate antiviral genes in CMV-specific cells, whereas TT-and C albicans-specific cells mainly up-regulated Th17 inflammatory response. Our data suggest a mechanism for the persistence of CMV-specific CD4 response and earlier loss of mucosal Th17-associated TT-and C albicans-specific CD4 response in AIDS.

Original languageEnglish (US)
Pages (from-to)1136-1144
Number of pages9
JournalBlood
Volume121
Issue number7
DOIs
StatePublished - Feb 14 2013
Externally publishedYes

Fingerprint

Tetanus Toxoid
T-cells
Pathogens
Transcriptome
Gene expression
HIV Infections
HIV-1
T-Lymphocytes
HIV
Chemokines
Antigens
Candida
DNA
Microarrays
Antiviral Agents
Microarray Analysis
Genes
Candida albicans
Acquired Immunodeficiency Syndrome
Up-Regulation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Distinct gene-expression profiles associated with the susceptibility of pathogen-specific CD4 T cells to HIV-1 infection. / Hu, Haitao; Nau, Martin; Ehrenberg, Phil; Chenine, Agnes Laurence; MacEdo, Camila; Zhou, Yu; Daye, Z. John; Wei, Zhi; Vahey, Maryanne; Michael, Nelson L.; Kim, Jerome H.; Marovich, Mary; Ratto-Kim, Silvia.

In: Blood, Vol. 121, No. 7, 14.02.2013, p. 1136-1144.

Research output: Contribution to journalArticle

Hu, H, Nau, M, Ehrenberg, P, Chenine, AL, MacEdo, C, Zhou, Y, Daye, ZJ, Wei, Z, Vahey, M, Michael, NL, Kim, JH, Marovich, M & Ratto-Kim, S 2013, 'Distinct gene-expression profiles associated with the susceptibility of pathogen-specific CD4 T cells to HIV-1 infection', Blood, vol. 121, no. 7, pp. 1136-1144. https://doi.org/10.1182/blood-2012-07-446278
Hu, Haitao ; Nau, Martin ; Ehrenberg, Phil ; Chenine, Agnes Laurence ; MacEdo, Camila ; Zhou, Yu ; Daye, Z. John ; Wei, Zhi ; Vahey, Maryanne ; Michael, Nelson L. ; Kim, Jerome H. ; Marovich, Mary ; Ratto-Kim, Silvia. / Distinct gene-expression profiles associated with the susceptibility of pathogen-specific CD4 T cells to HIV-1 infection. In: Blood. 2013 ; Vol. 121, No. 7. pp. 1136-1144.
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