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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Expression profile of host restriction factors in HIV-1 elite controllers
Retrovirology, Volume 10, No. 1, Article 106, Year 2013
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Description
Background: Several host-encoded antiviral factors suppress HIV-1 replication in a cell-autonomous fashion in vitro. The relevance of these defenses to the control of HIV-1 in vivo remains to be elucidated. We hypothesized that cellular restriction of HIV-1 replication plays a significant role in the observed suppression of HIV-1 in "elite controllers", individuals who maintain undetectable levels of viremia in the absence of antiretroviral therapy (ART). We comprehensively compared the expression levels of 34 host restriction factors and cellular activation levels in CD4+ T cells and sorted T cell subsets between elite controllers, HIV-1-infected (untreated) non-controllers, ART-suppressed, and uninfected individuals.Results: Expression of schlafen 11, a codon usage-based inhibitor of HIV-1 protein synthesis, was significantly elevated in CD4+ T cells from elite controllers as compared to both non-controllers (p = 0.048) and ART-suppressed individuals (p = 0.024), with this effect most apparent in central memory CD4+ T cells. Schlafen 11 expression levels were comparable between controllers and uninfected individuals. Cumulative restriction factor expression was positively correlated with CD4+ T cell activation (r2 = 0.597, p < 0.0001), viral load (r2 = 0.34, p = 0.015), and expression of ISG15 (r2 = 0.73, p < 0.0001), a marker of interferon exposure. APOBEC3C, APOBEC3D, CTR9, TRIM26, and TRIM32 were elevated in elite controllers with respect to ART-suppressed individuals, while levels were comparable to uninfected individuals and non-controllers.Conclusions: Host restriction factor expression typically scales with cellular activation levels. However, the elevated mRNA and protein expression of schlafen 11, despite low activation and viral load, violates the global pattern and may be a signature characteristic of HIV-1 elite control. © 2013 Abdel-Mohsen et al.; licensee BioMed Central Ltd.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3827935/bin/1742-4690-10-106-S1.docx
Authors & Co-Authors
Abdel-Mohsen, Mohamed T.
United States, San Francisco
Ucsf School of Medicine
Egypt, Cairo
College of Science
Raposo, Rui André S.
United States, San Francisco
University of California, San Francisco
Deng, Xutao
United States, San Francisco
Vitalant Research Institute
Li, Manqing
United States, San Diego
Department of Molecular Biology
Liegler, Teri J.
United States, San Francisco
Ucsf School of Medicine
Sinclair, Elizabeth
United States, San Francisco
Ucsf School of Medicine
Salama, M. S.
Egypt, Cairo
College of Science
Ghanem, Hussam E.A.
Egypt, Cairo
College of Science
Hoh, Rebeccah A.
United States, San Francisco
Ucsf School of Medicine
Wong, Joseph K.
United States, San Francisco
Ucsf School of Medicine
United States, San Francisco
San Francisco va Health Care System
David, Michael
United States, San Diego
Department of Molecular Biology
Nixon, Douglas F.
United States, San Francisco
University of California, San Francisco
Deeks, Steven G.
United States, San Francisco
Ucsf School of Medicine
Pillai, Satish K.
United States, San Francisco
Ucsf School of Medicine
United States, San Francisco
Vitalant Research Institute
United States, San Francisco
San Francisco va Health Care System
Statistics
Citations: 14
Authors: 14
Affiliations: 6
Identifiers
Doi:
10.1186/1742-4690-10-106
Research Areas
Genetics And Genomics
Infectious Diseases