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 Medjournal_title
Science translational medicineauthors
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 Ddoi
10.1126/scitranslmed.aag1048subject
Has Abstractpub_date
2016-09-28 00:00:00pages
358ra125issue
358eissn
1946-6234issn
1946-6242pii
8/358/358ra125journal_volume
8pub_type
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