Expression profile of host restriction factors in HIV-1 elite controllers
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- 作者：Mohamed Abdel-Mohsen (1) (5)
Rui André Saraiva Raposo (2)
Xutao Deng (3)
Manqing Li (4)
Teri Liegler (1)
Elizabeth Sinclair (1)
Mohamed S Salama (5)
Hussam El-din A Ghanem (5)
Rebecca Hoh (1)
Joseph K Wong (1) (6)
Michael David (4)
Douglas F Nixon (2)
Steven G Deeks (1)
Satish K Pillai (1) (3) (6) - 关键词：Elite controllers ; Intrinsic immunity ; Retroviral restriction factors ; APOBEC3 ; BST2/tetherin ; TRIM ; schlafen 11 ; p21 ; T cell activation
- 刊名：Retrovirology
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：10
- 期：1
- 全文大小：1,308 KB
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Rui André Saraiva Raposo (2)
Xutao Deng (3)
Manqing Li (4)
Teri Liegler (1)
Elizabeth Sinclair (1)
Mohamed S Salama (5)
Hussam El-din A Ghanem (5)
Rebecca Hoh (1)
Joseph K Wong (1) (6)
Michael David (4)
Douglas F Nixon (2)
Steven G Deeks (1)
Satish K Pillai (1) (3) (6)
1. Department of Medicine, University of California San Francisco, San Francisco, California, USA
5. Faculty of Science, Ain Shams University, Cairo, Egypt
2. Division of Experimental Medicine, University of California San Francisco, San Francisco, California, USA
3. Blood Systems Research Institute, San Francisco, California, USA
4. Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, La Jolla, California, USA
6. Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California, 94118-4417, USA - ISSN：1742-4690
文摘
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--.048) and ART-suppressed individuals (p--.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--.597, p-lt;-.0001), viral load (r2--.34, p--.015), and expression of ISG15 (r2--.73, p-lt;-.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.