Role of HIV-specific CD8(+) T cells in pediatric HIV cure strategies after widespread early viral escape
File(s)
Published version
Author(s)
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.
Date Issued
2017-10-05
Date Acceptance
2017-08-30
Citation
Journal of Experimental Medicine, 2017, 214 (11), pp.3239-3261
ISSN
0022-1007
Publisher
Rockefeller University 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/).
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000414604800008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
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
Publication Status
Published
Date Publish Online
2017-10-05