Expression profile of host restriction factors in HIV-1 elite controllers
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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 (r 2 = 0.597, p < 0.0001), viral load (r 2 = 0.34, p = 0.015), and expression of ISG15 (r 2 = 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.
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Schlafen 11 may play an important role in HIV-1 elite control in vivo.
“This is a unique property of Schlafen 11 among 34 known anti-HIV-1 factors tested (113) and suggests that Schlafen 11 may play an important role in HIV-1 elite control in vivo.”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [113]
Schlafen 11 is highly expressed in HIV-1 elite controllers compared with noncontrollers and ART-suppressed individuals.
“Interestingly, Schlafen 11 is highly expressed in HIV-1 elite controllers, individuals who have never been exposed to antiretroviral therapy (ART) but naturally suppress HIV-1 viral loads to an undetectable level, compared with noncontrollers and ART-suppressed individuals.”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [113]
This is a unique property of Schlafen 11 among 34 known anti-HIV-1 factors tested.
“This is a unique property of Schlafen 11 among 34 known anti-HIV-1 factors tested (113) and suggests that Schlafen 11 may play an important role in HIV-1 elite control in vivo.”
From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [113]
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“This is a unique property of Schlafen 11 among 34 known anti-HIV-1 factors tested (113) and suggests that Schlafen 11 may play an important role in HIV-1 elite control in vivo.”
BackgroundA Cell-Intrinsic Inhibitor of HIV-1 Reverse Transcription in CD4+ T Cells from Elite Controllers
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- Authors
- Abdel-Mohsen, M., Raposo, R. A. S., Deng, X., Li, M., Liegler, T., Sinclair, E., Salama, M. S., Ghanem, H. E.-D. A., Hoh, R., Wong, J. K., David, M., Nixon, D. F., Deeks, S. G., & Pillai, S. K.
- Affiliations
- University of California, San Francisco (US)
- Blood Systems Research Institute (US)
- University of California San Diego (US)
- Ain Shams University (EG)
- San Francisco VA Medical Center (US)
- Corresponding author
- Pillai, Satish K
- ORCID
- Venue
- Retrovirology
- Published
- 2013-10-16
- Volume
- 10
- Issue
- 1
- Pages
- 106-106
- ISSN
- 1742-4690 (ISSN-L)
- PMC
- PMC3827935
- OpenAlex
- W2141271993
- Cited by
- 96
- References
- 55
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 9 · 2017: 15 · 2016: 7 · 2015: 15 · 2014: 12 · 2013: 1
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Retrovirology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Delaney AIDS Research Enterprise (U19AI096109)
- National Institutes of Health (RR024131, AI027763)
- Center for AIDS Research, University of Washington (P30-AI027763, R24 AI067039)
- University of California, San Francisco (P30AI027763, UL1RR024131)
- National Institute of Mental Health (P30-MH62246, P30MH062246)
- National Institute on Drug Abuse (K01DA024654)
- National Institute of General Medical Sciences (R01GM101982)
- National Institute of Allergy and Infectious Diseases (K24AI069994, P01AI090935, U19AI096109, R21AI093179, R21 AI93179, R01AI087145, R24AI067039, P30AI027763)
- National Center for Research Resources (UL1RR024131)
- Center for AIDS Prevention Studies, University of California, San Francisco (P30 MH62246)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Keywords
- HIV-1 elite controllers, host restriction factors, Schlafen 11, CD4+ T cell activation, central memory T cells, ISG15, APOBEC3C, APOBEC3D, CTR9, TRIM26, TRIM32, viral load, antiretroviral therapy suppression
- MeSH terms
- Humans, Nuclear Proteins, Biomarkers, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, HIV Long-Term Survivors, Gene Expression Profiling
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