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Sci Transl Med. 2016 Sep 28;8(358):358ra125. doi: 10.1126/scitranslmed.aag1048.

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

Author information

1
Department of Paediatrics, Peter Medawar Building for Pathogen Research, South Parks Road, University of Oxford, Oxford OX1 3SY, U.K. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal (UKZN), Durban, South Africa. Max von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University Munich, Munich, Germany. German Center for Infection Research (DZIF), Partner Site Munich, Germany.
2
Department of Paediatrics, Peter Medawar Building for Pathogen Research, South Parks Road, University of Oxford, Oxford OX1 3SY, U.K.
3
Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
4
Institute for Emerging Infections, Oxford Martin School, University of Oxford, Oxford, U.K. Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, U.K. Oxford National Institute of Health Research, Biomedical Research Centre, Oxford, U.K.
5
Department of Paediatrics, Peter Medawar Building for Pathogen Research, South Parks Road, University of Oxford, Oxford OX1 3SY, U.K. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal (UKZN), Durban, South Africa.
6
Institute of Cancer Research, Old Brompton Road, London SW7 3RP, U.K.
7
Department of Mathematics, Ludwig-Maximilians-University Munich, Theresienstrasse 39, 80333 Munich, Germany.
8
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal (UKZN), Durban, South Africa.
9
Department of Paediatrics, Imperial College London, London, U.K.
10
Blizard Institute, Queen Mary University of London, London, U.K.
11
KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa. Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
12
Department of Paediatrics, Peter Medawar Building for Pathogen Research, South Parks Road, University of Oxford, Oxford OX1 3SY, U.K. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal (UKZN), Durban, South Africa. KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa.
13
KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa.
14
Department of Paediatric Infectious Diseases, Great Ormond Street Hospital for Children, London, U.K.
15
Paediatric Department, Kimberley Hospital, Northern Cape, South Africa.
16
Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, U.K. Oxford National Institute of Health Research, Biomedical Research Centre, Oxford, U.K.
17
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal (UKZN), Durban, South Africa. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139-4307, USA.
18
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal (UKZN), Durban, South Africa. KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), University of KwaZulu-Natal (UKZN), 4001 Durban, South Africa. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139-4307, USA. Max Planck Institute for Infection Biology, Berlin, Germany.
19
Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa. Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Center for the AIDS Programme of Research in South Africa (CAPRISA), 4001 Durban, South Africa.
20
Department of Paediatrics, Peter Medawar Building for Pathogen Research, South Parks Road, University of Oxford, Oxford OX1 3SY, U.K. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal (UKZN), Durban, South Africa. Department of Paediatric Infectious Diseases, Great Ormond Street Hospital for Children, London, U.K. philip.goulder@paediatrics.ox.ac.uk.

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.

PMID:
27683550
PMCID:
PMC6087524
DOI:
10.1126/scitranslmed.aag1048
[Indexed for MEDLINE]
Free PMC Article

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