Abstract
Identification of CMPK2 as an Interferon Stimulated Gene that Restricts HIV Infection
The Journal of immunology (1950), Vol.198(Supplement_1), pp.158-158.12
05/01/2017
DOI: 10.4049/jimmunol.198.Supp.158.12
Abstract
Type 1 interferons upregulate many interferon-stimulated genes (ISGs) with diverse antiviral effects. ISGs that restrict HIV in humans have been poorly characterized. Exogenous interferon-α decreases HIV viremia: we hypothesized that interferon-α induces expression of ISGs with anti-HIV activity in activated CD4+ T cells, the cells in which HIV chiefly replicates.
Activated CD4+ T cells (CD3+/CD4+/CD38+/HLA-DR+) were sorted from PBMCs taken from 19 HIV infected patients with uncontrolled viremia before and after peginterferon alpha 2b (IFN) administration. RNAseq was performed and ISGs were identified if they were up-regulated in 11/19 people. Viral kinetics were measured pre- and post-interferon and correlated with each ISG to identify putative HIV restriction factors. In vivo findings were tested in THP-1 cells. mRNA (measured by qPCR) and protein (measured by Western blot) were quantified pre- and post-IFNα treatment (1000 IU/mL). RNA interference was used to test whether the anti-HIV effect of IFNα could be attributable to CMPK2.
Among the 19 persons, 99 ISGs were defined in activated CD4+ T cells: the magnitude of upregulation of 13 ISGs correlated strongly with plasma HIV RNA decline (r>−0.8 for all, p<0.001 for all). Cytidine/Uridine Monophosphate Kinase 2 (CMPK2) was selected for examination. CMPK2 mRNA was upregulated by IFNα 40-fold, and protein upregulation was confirmed. IFNα restricted HIV replication in vitro 1000-fold, and siRNA knockdown of CMPK2 restored HIV replication to 72.1% of untreated cells (p=0.019).
CMPK2, a gene involved in maintenance of intracellular UTP/CTP, is an ISG with potential to restrict HIV replication. Future work will focus on the mechanism underlying the antiviral effects of CMPK2.
Details
- Title: Subtitle
- Identification of CMPK2 as an Interferon Stimulated Gene that Restricts HIV Infection
- Creators
- Mary SolimanRamy El-DiwanySarah WheelanDavid L ThomasAshwin Balagopal
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.198(Supplement_1), pp.158-158.12
- DOI
- 10.4049/jimmunol.198.Supp.158.12
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2017
- Academic Unit
- Surgery
- Record Identifier
- 9984966715302771
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