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Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication.

dc.contributor.author Cohen, MS
dc.contributor.author Crump, John Andrew
dc.contributor.author Cunningham, Coleen
dc.contributor.author Denny, Thomas Norton
dc.contributor.author Ding, Haitao
dc.contributor.author Ferrari, Guido
dc.contributor.author Freel, SA
dc.contributor.author Haynes, Barton Ford
dc.contributor.author Kappes, JC
dc.contributor.author Kirchherr, JL
dc.contributor.author McMichael, Andrew J
dc.contributor.author Ochsenbauer, C
dc.contributor.author Picking, RA
dc.contributor.author Soderberg, Kelly
dc.contributor.author Tomaras, Georgia Doris
dc.contributor.author Weinhold, Kent James
dc.coverage.spatial United States
dc.date.accessioned 2017-03-02T19:18:41Z
dc.date.available 2017-03-02T19:18:41Z
dc.date.issued 2012-06
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/22514337
dc.identifier JVI.00437-12
dc.identifier.uri https://hdl.handle.net/10161/13786
dc.description.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.
dc.language eng
dc.relation.ispartof J Virol
dc.relation.isversionof 10.1128/JVI.00437-12
dc.subject Adult
dc.subject CD8-Positive T-Lymphocytes
dc.subject Cells, Cultured
dc.subject Cohort Studies
dc.subject Down-Regulation
dc.subject Female
dc.subject HIV Antigens
dc.subject HIV Infections
dc.subject HIV-1
dc.subject Humans
dc.subject Male
dc.subject Middle Aged
dc.subject Virus Replication
dc.subject Young Adult
dc.title Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/22514337
pubs.begin-page 6835
pubs.end-page 6846
pubs.issue 12
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Human Vaccine Institute
pubs.organisational-group Global Health Institute
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Duke Human Vaccine Institute
pubs.organisational-group Medicine, Infectious Diseases
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Pathology
pubs.organisational-group Pediatrics
pubs.organisational-group Pediatrics, Infectious Diseases
pubs.organisational-group School of Medicine
pubs.organisational-group Staff
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Sciences
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 86
dc.identifier.eissn 1098-5514


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