Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication.
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 contrib...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2012
|
| _version_ | 1797063116516753408 |
|---|---|
| author | Freel, SA Picking, R Ferrari, G Ding, H Ochsenbauer, C Kappes, J Kirchherr, J Soderberg, K Weinhold, K Cunningham, C Denny, T Crump, J Cohen, MS Mcmichael, A Haynes, B Tomaras, G |
| author_facet | Freel, SA Picking, R Ferrari, G Ding, H Ochsenbauer, C Kappes, J Kirchherr, J Soderberg, K Weinhold, K Cunningham, C Denny, T Crump, J Cohen, MS Mcmichael, A Haynes, B Tomaras, G |
| author_sort | Freel, SA |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T20:55:14Z |
| format | Journal article |
| id | oxford-uuid:3900bd62-8d1b-4f0f-8908-3d6e396e9449 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:55:14Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:3900bd62-8d1b-4f0f-8908-3d6e396e94492022-03-26T13:53:08ZInitial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3900bd62-8d1b-4f0f-8908-3d6e396e9449EnglishSymplectic Elements at Oxford2012Freel, SAPicking, RFerrari, GDing, HOchsenbauer, CKappes, JKirchherr, JSoderberg, KWeinhold, KCunningham, CDenny, TCrump, JCohen, MSMcmichael, AHaynes, BTomaras, GCD8-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. |
| spellingShingle | Freel, SA Picking, R Ferrari, G Ding, H Ochsenbauer, C Kappes, J Kirchherr, J Soderberg, K Weinhold, K Cunningham, C Denny, T Crump, J Cohen, MS Mcmichael, A Haynes, B Tomaras, G Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication. |
| title | Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication. |
| title_full | Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication. |
| title_fullStr | Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication. |
| title_full_unstemmed | Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication. |
| title_short | Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication. |
| title_sort | initial hiv 1 antigen specific cd8 t cells in acute hiv 1 infection inhibit transmitted founder virus replication |
| work_keys_str_mv | AT freelsa initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT pickingr initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT ferrarig initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT dingh initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT ochsenbauerc initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT kappesj initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT kirchherrj initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT soderbergk initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT weinholdk initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT cunninghamc initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT dennyt initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT crumpj initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT cohenms initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT mcmichaela initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT haynesb initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication AT tomarasg initialhiv1antigenspecificcd8tcellsinacutehiv1infectioninhibittransmittedfoundervirusreplication |