Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection

Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventin...

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Main Authors: Muenchhoff, M, Adland, E, Karimanzira, O, Crowther, C, Pace, M, Csala, A, Leitman, E, Moonsamy, A, McGregor, C, Hurst, J, Groll, A, Mori, M, Sinmyee, S, Thobakgale, C, Tudor-Williams, G, Prendergast, A, Kloverpris, H, Roider, J, Leslie, A, Shingadia, D, Brits, T, Daniels, S, Frater, J, Willberg, C, Walker, B, Ndung'u, T, Jooste, P, Moore, P, Morris, L, Goulder, P
Format: Journal article
Language:English
Published: American Association for the Advancement of Science 2016
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author Muenchhoff, M
Adland, E
Karimanzira, O
Crowther, C
Pace, M
Csala, A
Leitman, E
Moonsamy, A
McGregor, C
Hurst, J
Groll, A
Mori, M
Sinmyee, S
Thobakgale, C
Tudor-Williams, G
Prendergast, A
Kloverpris, H
Roider, J
Leslie, A
Shingadia, D
Brits, T
Daniels, S
Frater, J
Willberg, C
Walker, B
Ndung'u, T
Jooste, P
Moore, P
Morris, L
Goulder, P
author_facet Muenchhoff, M
Adland, E
Karimanzira, O
Crowther, C
Pace, M
Csala, A
Leitman, E
Moonsamy, A
McGregor, C
Hurst, J
Groll, A
Mori, M
Sinmyee, S
Thobakgale, C
Tudor-Williams, G
Prendergast, A
Kloverpris, H
Roider, J
Leslie, A
Shingadia, D
Brits, T
Daniels, S
Frater, J
Willberg, C
Walker, B
Ndung'u, T
Jooste, P
Moore, P
Morris, L
Goulder, P
author_sort Muenchhoff, M
collection OXFORD
description Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-naïve children aged >5 years maintaining normal-for-age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26,000 copies/ml). Potent, broadly neutralizing antibody responses in most of the subjects and strong virus-specific T cell activity were present but did not drive pediatric nonprogression. However, reduced CCR5 expression and low HIV infection in long-lived central memory CD4 T cells were observed in pediatric nonprogressors. These children therefore express two cardinal immunological features of nonpathogenic SIV infection in sooty mangabeys-low immune activation despite high viremia and low CCR5 expression on long-lived central memory CD4 T cells-suggesting closer similarities with nonpathogenetic mechanisms evolved over thousands of years in natural SIV hosts than those operating in HIV-infected adults.
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spelling oxford-uuid:ac603e9b-00b1-4835-b5c9-32eaf482b09f2022-03-27T03:28:52ZNonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ac603e9b-00b1-4835-b5c9-32eaf482b09fEnglishSymplectic Elements at OxfordAmerican Association for the Advancement of Science2016Muenchhoff, MAdland, EKarimanzira, OCrowther, CPace, MCsala, ALeitman, EMoonsamy, AMcGregor, CHurst, JGroll, AMori, MSinmyee, SThobakgale, CTudor-Williams, GPrendergast, AKloverpris, HRoider, JLeslie, AShingadia, DBrits, TDaniels, SFrater, JWillberg, CWalker, BNdung'u, TJooste, PMoore, PMorris, LGoulder, PDisease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-naïve children aged >5 years maintaining normal-for-age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26,000 copies/ml). Potent, broadly neutralizing antibody responses in most of the subjects and strong virus-specific T cell activity were present but did not drive pediatric nonprogression. However, reduced CCR5 expression and low HIV infection in long-lived central memory CD4 T cells were observed in pediatric nonprogressors. These children therefore express two cardinal immunological features of nonpathogenic SIV infection in sooty mangabeys-low immune activation despite high viremia and low CCR5 expression on long-lived central memory CD4 T cells-suggesting closer similarities with nonpathogenetic mechanisms evolved over thousands of years in natural SIV hosts than those operating in HIV-infected adults.
spellingShingle Muenchhoff, M
Adland, E
Karimanzira, O
Crowther, C
Pace, M
Csala, A
Leitman, E
Moonsamy, A
McGregor, C
Hurst, J
Groll, A
Mori, M
Sinmyee, S
Thobakgale, C
Tudor-Williams, G
Prendergast, A
Kloverpris, H
Roider, J
Leslie, A
Shingadia, D
Brits, T
Daniels, S
Frater, J
Willberg, C
Walker, B
Ndung'u, T
Jooste, P
Moore, P
Morris, L
Goulder, P
Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection
title Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection
title_full Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection
title_fullStr Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection
title_full_unstemmed Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection
title_short Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection
title_sort nonprogressing hiv infected children share fundamental immunological features of nonpathogenic siv infection
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