Long-term passage of Vif-null HIV-1 in CD4+ T cells expressing sub-lethal levels of APOBEC proteins fails to develop APOBEC resistance

Abstract APOBEC3G (A3G) is a cytidine deaminase with potent antiviral activity that is antagonized by Vif. A3G is expressed in a cell type-specific manner and some semi-permissive cells, including A3.01, express A3G but fail to block replication of Vif-null HIV-1. Here we explored the semi-permissiv...

Full description

Saved in:
Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2017-04, Vol.504, p.1-11
Main Authors: Miyagi, Eri, Kao, Sandra, Fumitaka, Miyoshi, Buckler-White, Alicia, Plishka, Ron, Strebel, Klaus
Format: Article
Language:English
Subjects:
A3.01 cells
Antiviral resistance
APOBEC-3G Deaminase - antagonists & inhibitors
APOBEC-3G Deaminase - genetics
APOBEC-3G Deaminase - metabolism
APOBEC3G
Base Sequence
CD4-Positive T-Lymphocytes - virology
Cell Line, Tumor
Child, Preschool
Cytidine deaminase
Deamination
Female
HEK293 Cells
HeLa Cells
HIV Infections - virology
HIV-1
HIV-1 - genetics
Humans
Hypermutation
Infectious Disease
Jurkat Cells
Proviruses - genetics
Proviruses - growth & development
Purifying selection
RNA Interference
RNA, Small Interfering - genetics
RNA, Viral - genetics
Sequence Analysis, RNA
Vif
vif Gene Products, Human Immunodeficiency Virus - genetics
vif Gene Products, Human Immunodeficiency Virus - metabolism
Viral evolution
Virus Replication - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract APOBEC3G (A3G) is a cytidine deaminase with potent antiviral activity that is antagonized by Vif. A3G is expressed in a cell type-specific manner and some semi-permissive cells, including A3.01, express A3G but fail to block replication of Vif-null HIV-1. Here we explored the semi-permissive nature of A3.01 cells and found it to be defined exclusively by the levels of A3G. Indeed, minor changes in A3G levels rendered A3.01 cells either fully permissive or non-permissive for Vif-null HIV-1. Our data indicate that A3.01 cells express sub-lethal levels of catalytically active A3G that affects Vif-null HIV-1 at the proviral level but does not completely block virus replication due to purifying selection. Attempts to use the selective pressure exerted by such sub-lethal levels of A3G to select for APOBEC-resistant Vif-null virus capable of replicating in H9 cells failed despite passaging virus for five months, demonstrating that Vif is a critical viral accessory protein.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2017.01.016