HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occur...

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Manylion Llyfryddiaeth
Prif Awduron: Altfeld, M, Allen, T, Yu, X, Johnston, M, Agrawal, D, Korber, B, Montefiori, D, O'Connor, D, Davis, B, Lee, P, Maier, E, Harlow, J, Goulder, P, Brander, C, Rosenberg, E, Walker, B
Fformat: Journal article
Iaith:English
Cyhoeddwyd: 2002
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author Altfeld, M
Allen, T
Yu, X
Johnston, M
Agrawal, D
Korber, B
Montefiori, D
O'Connor, D
Davis, B
Lee, P
Maier, E
Harlow, J
Goulder, P
Brander, C
Rosenberg, E
Walker, B
author_facet Altfeld, M
Allen, T
Yu, X
Johnston, M
Agrawal, D
Korber, B
Montefiori, D
O'Connor, D
Davis, B
Lee, P
Maier, E
Harlow, J
Goulder, P
Brander, C
Rosenberg, E
Walker, B
author_sort Altfeld, M
collection OXFORD
description Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.
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spelling oxford-uuid:248a78e7-58b1-4094-8c39-169f9c1eaec62022-03-26T11:50:32ZHIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:248a78e7-58b1-4094-8c39-169f9c1eaec6EnglishSymplectic Elements at Oxford2002Altfeld, MAllen, TYu, XJohnston, MAgrawal, DKorber, BMontefiori, DO'Connor, DDavis, BLee, PMaier, EHarlow, JGoulder, PBrander, CRosenberg, EWalker, BEarly treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.
spellingShingle Altfeld, M
Allen, T
Yu, X
Johnston, M
Agrawal, D
Korber, B
Montefiori, D
O'Connor, D
Davis, B
Lee, P
Maier, E
Harlow, J
Goulder, P
Brander, C
Rosenberg, E
Walker, B
HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.
title HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.
title_full HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.
title_fullStr HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.
title_full_unstemmed HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.
title_short HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.
title_sort hiv 1 superinfection despite broad cd8 t cell responses containing replication of the primary virus
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