Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.
In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therap...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-02-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347345/pdf/?tool=EBI |
| _version_ | 1818837951553994752 |
|---|---|
| author | Guido Ferrari Bette Korber Nilu Goonetilleke Michael K P Liu Emma L Turnbull Jesus F Salazar-Gonzalez Natalie Hawkins Steve Self Sydeaka Watson Michael R Betts Cynthia Gay Kara McGhee Pierre Pellegrino Ian Williams Georgia D Tomaras Barton F Haynes Clive M Gray Persephone Borrow Mario Roederer Andrew J McMichael Kent J Weinhold |
| author_facet | Guido Ferrari Bette Korber Nilu Goonetilleke Michael K P Liu Emma L Turnbull Jesus F Salazar-Gonzalez Natalie Hawkins Steve Self Sydeaka Watson Michael R Betts Cynthia Gay Kara McGhee Pierre Pellegrino Ian Williams Georgia D Tomaras Barton F Haynes Clive M Gray Persephone Borrow Mario Roederer Andrew J McMichael Kent J Weinhold |
| author_sort | Guido Ferrari |
| collection | DOAJ |
| description | In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therapy-naïve subjects were studied in detail between 1 and 87 weeks following onset of symptoms of acute HIV-1 infection. Synthetic peptides representing the autologous transmitted/founder HIV-1 sequences were used in multiparameter flow cytometry assays to determine the functionality of HIV-1-specific CD8+ T memory cells. In all seven patients, the earliest T cell responses were predominantly oligofunctional, although the relative contribution of multifunctional cell responses increased significantly with time from infection. Interestingly, only the magnitude of the total and not of the poly-functional T-cell responses was significantly associated with the selection of escape mutants. However, the high contribution of MIP-1β-producing CD8+ T-cells to the total response suggests that mechanisms not limited to cytotoxicity could be exerting immune pressure during acute infection. Lastly, we show that epitope entropy, reflecting the capacity of the epitope to tolerate mutational change and defined as the diversity of epitope sequences at the population level, was also correlated with rate of emergence of escape mutants. |
| first_indexed | 2024-12-19T03:30:40Z |
| format | Article |
| id | doaj.art-a23efb6b873d445da5c85d22e3a5462f |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-19T03:30:40Z |
| publishDate | 2011-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-a23efb6b873d445da5c85d22e3a5462f2022-12-21T20:37:30ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742011-02-0172e100127310.1371/journal.ppat.1001273Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.Guido FerrariBette KorberNilu GoonetillekeMichael K P LiuEmma L TurnbullJesus F Salazar-GonzalezNatalie HawkinsSteve SelfSydeaka WatsonMichael R BettsCynthia GayKara McGheePierre PellegrinoIan WilliamsGeorgia D TomarasBarton F HaynesClive M GrayPersephone BorrowMario RoedererAndrew J McMichaelKent J WeinholdIn the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therapy-naïve subjects were studied in detail between 1 and 87 weeks following onset of symptoms of acute HIV-1 infection. Synthetic peptides representing the autologous transmitted/founder HIV-1 sequences were used in multiparameter flow cytometry assays to determine the functionality of HIV-1-specific CD8+ T memory cells. In all seven patients, the earliest T cell responses were predominantly oligofunctional, although the relative contribution of multifunctional cell responses increased significantly with time from infection. Interestingly, only the magnitude of the total and not of the poly-functional T-cell responses was significantly associated with the selection of escape mutants. However, the high contribution of MIP-1β-producing CD8+ T-cells to the total response suggests that mechanisms not limited to cytotoxicity could be exerting immune pressure during acute infection. Lastly, we show that epitope entropy, reflecting the capacity of the epitope to tolerate mutational change and defined as the diversity of epitope sequences at the population level, was also correlated with rate of emergence of escape mutants.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347345/pdf/?tool=EBI |
| spellingShingle | Guido Ferrari Bette Korber Nilu Goonetilleke Michael K P Liu Emma L Turnbull Jesus F Salazar-Gonzalez Natalie Hawkins Steve Self Sydeaka Watson Michael R Betts Cynthia Gay Kara McGhee Pierre Pellegrino Ian Williams Georgia D Tomaras Barton F Haynes Clive M Gray Persephone Borrow Mario Roederer Andrew J McMichael Kent J Weinhold Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection. PLoS Pathogens |
| title | Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection. |
| title_full | Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection. |
| title_fullStr | Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection. |
| title_full_unstemmed | Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection. |
| title_short | Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection. |
| title_sort | relationship between functional profile of hiv 1 specific cd8 t cells and epitope variability with the selection of escape mutants in acute hiv 1 infection |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347345/pdf/?tool=EBI |
| work_keys_str_mv | AT guidoferrari relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT bettekorber relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT nilugoonetilleke relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT michaelkpliu relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT emmalturnbull relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT jesusfsalazargonzalez relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT nataliehawkins relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT steveself relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT sydeakawatson relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT michaelrbetts relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT cynthiagay relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT karamcghee relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT pierrepellegrino relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT ianwilliams relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT georgiadtomaras relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT bartonfhaynes relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT clivemgray relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT persephoneborrow relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT marioroederer relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT andrewjmcmichael relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection AT kentjweinhold relationshipbetweenfunctionalprofileofhiv1specificcd8tcellsandepitopevariabilitywiththeselectionofescapemutantsinacutehiv1infection |