title: Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication.
abstract: CD8-mediated virus inhibition can be detected in HIV-1-positive subjects who naturally control virus replication. Characterizing the inhibitory function of CD8(+) T cells during acute HIV-1 infection (AHI) can elucidate the nature of the CD8(+) responses that can be rapidly elicited and that contribute to virus control. We examined the timing and HIV-1 antigen specificity of antiviral CD8(+) T cells during AHI. Autologous and heterologous CD8(+) T cell antiviral functions were assessed longitudinally during AHI in five donors from the CHAVI 001 cohort using a CD8(+) T cell-mediated virus inhibition assay (CD8 VIA) and transmitted/founder (T/F) viruses. Potent CD8(+) antiviral responses against heterologous T/F viruses appeared during AHI at the first time point sampled in each of the 5 donors (Fiebig stages 1/2 to 5). Inhibition of an autologous T/F virus was durable to 48 weeks; however, inhibition of heterologous responses declined concurrent with the resolution of viremia. HIV-1 viruses from 6 months postinfection were more resistant to CD8(+)-mediated virus inhibition than cognate T/F viruses, demonstrating that the virus escapes early from CD8(+) T cell-mediated inhibition of virus replication. CD8(+) T cell antigen-specific subsets mediated inhibition of T/F virus replication via soluble components, and these soluble responses were stimulated by peptide pools that include epitopes that were shown to drive HIV-1 escape during AHI. These data provide insights into the mechanisms of CD8-mediated virus inhibition and suggest that functional analyses will be important for determining whether similar antigen-specific virus inhibition can be induced by T cell-directed vaccine strategies.
authors.affiliation: Department of Surgery, Duke University Human Vaccine Institute, Durham, North Carolina, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Freel
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Picking
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Haitao
authors.initials: H
authors.lastname: Ding
authors.forename: Christina
authors.initials: C
authors.lastname: Ochsenbauer
authors.forename: John C
authors.initials: JC
authors.lastname: Kappes
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kirchherr
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Soderberg
authors.forename: Kent J
authors.initials: KJ
authors.lastname: Weinhold
authors.forename: Coleen K
authors.initials: CK
authors.lastname: Cunningham
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Denny
authors.forename: John A
authors.initials: JA
authors.lastname: Crump
authors.forename: Myron S
authors.initials: MS
authors.lastname: Cohen
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D015331:Cohort Studies; D015536:Down-Regulation; D005260:Female; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D014779:Virus Replication; D055815:Young Adult
chemical_list: D015488:HIV Antigens