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dc.contributor.authorNaranbhai, Vivek
dc.contributor.authorAltfeld, Marcus
dc.contributor.authorKarim, Salim S. Abdool
dc.contributor.authorNdung'u, Thumbi
dc.contributor.authorKarim, Quarraisha Abdool
dc.contributor.authorCarr, William H.
dc.date.accessioned2013-05-13T20:22:32Z
dc.date.issued2013
dc.identifier.citationNaranbhai, Vivek, Marcus Altfeld, Salim S. Abdool Karim, Thumbi Ndung'u, Quarraisha Abdool Karim, and William H. Carr. 2013. Changes in natural killer cell activation and function during primary HIV-1 infection. PLoS ONE 8(1): e53251.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10622997
dc.description.abstractBackground: Recent reports suggest that Natural Killer (NK) cells may modulate pathogenesis of primary HIV-1 infection. However, HIV dysregulates NK-cell responses. We dissected this bi-directional relationship to understand how HIV impacts NK-cell responses during primary HIV-1 infection. Methodology/Principal Findings: Paired samples from 41 high-risk, initially HIV-uninfected CAPRISA004 participants were analysed prior to HIV acquisition, and during viraemic primary HIV-1 infection. At the time of sampling post-infection five women were seronegative, 11 women were serodiscordant, and 25 women were seropositive by HIV-1 rapid immunoassay. Flow cytometry was used to measure NK and T-cell activation, NK-cell receptor expression, cytotoxic and cytokine-secretory functions, and trafficking marker expression (CCR7, α\(_4\)β\(_7\)). Non-parametric statistical tests were used. Both NK cells and T-cells were significantly activated following HIV acquisition (p = 0.03 and p<0.0001, respectively), but correlation between NK-cell and T-cell activation was uncoupled following infection (pre-infection r = 0.68;p<0.0001; post-infection, during primary infection r = 0.074;p = 0.09). Nonetheless, during primary infection NK-cell and T-cell activation correlated with HIV viral load (r = 0.32'p = 0.04 and r = 0.35;p = 0.02, respectively). The frequency of Killer Immunoglobulin-like Receptor-expressing (KIR\(_{pos}\)) NK cells increased following HIV acquisition (p = 0.006), and KIR\(_{pos}\) NK cells were less activated than KIR\(_{neg}\) NK cells amongst individuals sampled while seronegative or serodiscordant (p = 0.001;p<0.0001 respectively). During HIV-1 infection, cytotoxic NK cell responses evaluated after IL-2 stimulation alone, or after co-culture with 721 cells, were impaired (p = 0.006 and p = 0.002, respectively). However, NK-cell IFN-y secretory function was not significantly altered. The frequency of CCR7+ NK cells was elevated during primary infection, particularly at early time-points (p<0.0001). Conclusions/Significance: Analyses of immune cells before and after HIV infection revealed an increase in both NK-cell activation and KIR expression, but reduced cytotoxicity during acute infection. The increase in frequency of NK cells able to traffic to lymph nodes following HIV infection suggests that these cells may play a role in events in secondary lymphoid tissue.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0053251en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541400/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectImmunologyen_US
dc.subjectImmune Cellsen_US
dc.subjectNK cellsen_US
dc.subjectT Cellsen_US
dc.subjectImmunityen_US
dc.subjectImmunity to Infectionsen_US
dc.subjectImmunopathologyen_US
dc.subjectMedicineen_US
dc.subjectInfectious Diseasesen_US
dc.subjectSexually Transmitted Diseasesen_US
dc.subjectAIDSen_US
dc.subjectHerpes Simplexen_US
dc.subjectViral Diseasesen_US
dc.subjectHIVen_US
dc.subjectRetrovirology and HIV immunopathogenesisen_US
dc.titleChanges in Natural Killer Cell Activation and Function during Primary HIV-1 Infectionen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorAltfeld, Marcus
dc.date.available2013-05-13T20:22:32Z
dc.identifier.doi10.1371/journal.pone.0053251*
dash.authorsorderedfalse
dash.contributor.affiliatedAltfeld, Marcus


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