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

Abstract:

: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.

journal_name

Sci Transl Med

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 AJ,Kloverpris H,Roider J,Leslie A,Shingadia D

doi

10.1126/scitranslmed.aag1048

subject

Has Abstract

pub_date

2016-09-28 00:00:00

pages

358ra125

issue

358

eissn

1946-6234

issn

1946-6242

pii

8/358/358ra125

journal_volume

8

pub_type

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