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, Zhongyin J Daye, Zhi Wei, Maryanne Vahey, Nelson L. Michael, Jerome H. Kim, Mary Marovich, Silvia Ratto-Kim

Research output: Contribution to journalArticle

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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

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

Hu, H., Nau, M., Ehrenberg, P., Chenine, A. L., MacEdo, C., Zhou, Y., ... Ratto-Kim, S. (2013). Distinct gene-expression profiles associated with the susceptibility of pathogen-specific CD4 T cells to HIV-1 infection. Blood, 121(7), 1136-1144. https://doi.org/10.1182/blood-2012-07-446278

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, Zhongyin J; 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, Zhongyin J ; 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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