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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 Freel, SA
dc.contributor.author Picking, RA
dc.contributor.author Ferrari, G
dc.contributor.author Ding, H
dc.contributor.author Ochsenbauer, C
dc.contributor.author Kappes, JC
dc.contributor.author Kirchherr, J
dc.contributor.author Soderberg, K
dc.contributor.author Weinhold, KJ
dc.contributor.author Cunningham, CK
dc.contributor.author Denny, T
dc.contributor.author Crump, JA
dc.contributor.author Cohen, MS
dc.contributor.author McMichael, AJ
dc.contributor.author Haynes, BF
dc.contributor.author Tomaras, GD
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.publisher American Society for Microbiology
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
duke.contributor.id Freel, SA|0297704
duke.contributor.id Ferrari, G|0108355
duke.contributor.id Weinhold, KJ|0099279
duke.contributor.id Cunningham, CK|0308797
duke.contributor.id Denny, T|0400543
duke.contributor.id Crump, JA|0231646
duke.contributor.id Haynes, BF|0114780
duke.contributor.id Tomaras, GD|0204832
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
duke.contributor.orcid Ferrari, G|0000-0001-7747-3349
duke.contributor.orcid Cunningham, CK|0000-0002-7725-3052
duke.contributor.orcid Tomaras, GD|0000-0001-8076-1931


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