Murine leukemia virus resists producer cell APOBEC3A by its Glycosylated Gag but not target cell APOBEC3A.

Autor: Jaguva Vasudevan AA; Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225, Düsseldorf, Germany. Electronic address: anand.jaguvavasudevan@nih.gov., Balakrishnan K; Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225, Düsseldorf, Germany; Department of Biochemistry, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, India., Franken A; Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225, Düsseldorf, Germany., Krikoni A; Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225, Düsseldorf, Germany., Häussinger D; Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225, Düsseldorf, Germany., Luedde T; Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225, Düsseldorf, Germany., Münk C; Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225, Düsseldorf, Germany. Electronic address: carsten.muenk@med.uni-duesseldorf.de.
Jazyk: angličtina
Zdroj: Virology [Virology] 2021 May; Vol. 557, pp. 1-14. Date of Electronic Publication: 2021 Feb 04.
DOI: 10.1016/j.virol.2021.01.017
Abstrakt: The human APOBEC3A (A3A) polynucleotide cytidine deaminase has been shown to have antiviral activity against HTLV-1 but not HIV-1, when expressed in the virus producer cell. In viral target cells, high levels of endogenous A3A activity have been associated with the restriction of HIV-1 during infection. Here we demonstrate that A3A derived from both target cells and producer cells can block the infection of Moloney-MLV (MLV) and related AKV-derived strains of MLV in a deaminase-dependent mode. Furthermore, glycosylated Gag (glycoGag) of MLV inhibits the encapsidation of human A3A, but target cell A3A was not affected by glycoGag and exerted deamination of viral DNA. Importantly, our results clearly indicate that poor glycoGag expression in MLV gag-pol packaging constructs as compared to abundant levels in full-length amphotropic MLV makes these viral vectors sensitive to A3A-mediated restriction. This raises the possibility of acquiring A3A-induced mutations in retroviral gene therapy applications.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: