Role of HIV-specific CD8(+) T cells in pediatric HIV cure strategies after widespread early viral escape

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Title: Role of HIV-specific CD8(+) T cells in pediatric HIV cure strategies after widespread early viral escape
Author(s): Leitman, EM
Thobakgale, CF
Adland, E
Ansari, MA
Raghwani, J
Prendergast, AJ
Tudor-Williams, G
Kiepiela, P
Hemelaar, J
Brener, J
Tsai, M-H
Mori, M
Riddell, L
Luzzi, G
Jooste, P
Ndung'u, T
Walker, BD
Pybus, OG
Kellam, P
Naranbhai, V
Matthews, PC
Gall, A
Goulder, PJR
Item Type: Journal Article
Abstract: Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in “shock-and-kill” cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to “corner” the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection.
Publication Date: 5-Oct-2017
Date of Acceptance: 30-Aug-2017
URI: http://hdl.handle.net/10044/1/59981
DOI: https://dx.doi.org/10.1084/jem.20162123
ISSN: 0022-1007
Publisher: ROCKEFELLER UNIV PRESS
Start Page: 3239
End Page: 3261
Journal / Book Title: JOURNAL OF EXPERIMENTAL MEDICINE
Volume: 214
Issue: 11
Copyright Statement: © 2017 Leitman et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
IMMUNODEFICIENCY-VIRUS TYPE-1
HLA CLASS-I
ACTIVE ANTIRETROVIRAL THERAPY
CELLULAR IMMUNE-RESPONSES
ORIGINAL ANTIGENIC SIN
LYMPHOCYTE RESPONSES
SELECTION PRESSURE
REPLICATION CAPACITY
HIV-1-INFECTED CHILDREN
DISEASE PROGRESSION
Adult
CD8-Positive T-Lymphocytes
Child
Child, Preschool
Epitopes, T-Lymphocyte
HIV Infections
HIV-1
HLA Antigens
Host-Pathogen Interactions
Humans
Immune Evasion
Interferon-gamma
T-Lymphocytes, Cytotoxic
Viral Load
gag Gene Products, Human Immunodeficiency Virus
CD8-Positive T-Lymphocytes
T-Lymphocytes, Cytotoxic
Humans
HIV-1
HIV Infections
HLA Antigens
Epitopes, T-Lymphocyte
Viral Load
Adult
Child
Child, Preschool
gag Gene Products, Human Immunodeficiency Virus
Host-Pathogen Interactions
Interferon-gamma
Immune Evasion
Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
IMMUNODEFICIENCY-VIRUS TYPE-1
HLA CLASS-I
ACTIVE ANTIRETROVIRAL THERAPY
CELLULAR IMMUNE-RESPONSES
ORIGINAL ANTIGENIC SIN
LYMPHOCYTE RESPONSES
SELECTION PRESSURE
REPLICATION CAPACITY
HIV-1-INFECTED CHILDREN
DISEASE PROGRESSION
11 Medical And Health Sciences
Immunology
Publication Status: Published
Online Publication Date: 2017-10-05
Appears in Collections:Department of Medicine
Faculty of Medicine



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