Article open access publication

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

Science Translational Medicine, American Association for the Advancement of Science (AAAS), ISSN 1946-6234

Volume 8, 358, 2016

DOI:10.1126/scitranslmed.aag1048, Dimensions: pub.1005451244, PMC: PMC6087524, PMID: 27683550,

Affiliations

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  1. (1) German Center for Infection Research, grid.452463.2
  2. (2) Ludwig Maximilian University of Munich, grid.5252.0
  3. (3) University of Oxford, grid.4991.5
  4. (4) University of KwaZulu-Natal, grid.16463.36
  5. (5) National Health Laboratory Service, grid.416657.7
  6. (6) Oxford National Institute of Health Research, Biomedical Research Centre, Oxford, U.K
  7. (7) Institute of Cancer Research, grid.18886.3f
  8. (8) Imperial College London, grid.7445.2
  9. (9) Queen Mary University of London, grid.4868.2
  10. (10) University of Copenhagen, grid.5254.6, KU
  11. (11) Great Ormond Street Hospital, grid.420468.c
  12. (12) Paediatric Department, Kimberley Hospital, Northern Cape, South Africa
  13. (13) Ragon Institute of MGH, MIT and Harvard, grid.461656.6
  14. (14) Max Planck Institute for Infection Biology, grid.418159.0
  15. (15) Center for the AIDS Programme of Research in South Africa (CAPRISA), 4001 Durban, South Africa
  16. (16) University of the Witwatersrand, grid.11951.3d

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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Times Cited: 63

Field Citation Ratio (FCR): 12.77

Relative Citation ratio (RCR): 3.67

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