title: Distinct gene-expression profiles associated with the susceptibility of pathogen-specific CD4 T cells to HIV-1 infection.
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 CFSE(low) 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 CFSE(low) 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.
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD;
authors.forename: Haitao
authors.initials: H
authors.lastname: Hu
authors.forename: Martin
authors.initials: M
authors.lastname: Nau
authors.forename: Phil
authors.initials: P
authors.lastname: Ehrenberg
authors.forename: Agnes-Laurence
authors.initials: AL
authors.lastname: Chenine
authors.forename: Camila
authors.initials: C
authors.lastname: Macedo
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Z John
authors.initials: ZJ
authors.lastname: Daye
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wei
authors.forename: Maryanne
authors.initials: M
authors.lastname: Vahey
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.forename: Mary
authors.initials: M
authors.lastname: Marovich
authors.forename: Silvia
authors.initials: S
authors.lastname: Ratto-Kim
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002176:Candida albicans / Q000276:immunology / Q000472:pathogenicity; D003587:Cytomegalovirus / Q000276:immunology / Q000472:pathogenicity; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D018928:Immunity, Mucosal / Q000235:genetics; D013745:Tetanus Toxoid / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology / Q000821:virology; D059467:Transcriptome; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D013745:Tetanus Toxoid