Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-8163

Knoepfel, S A; Salisch, N C; Huelsmann, P M; Rauch, P; Walter, H; Metzner, K J (2008). Comparison of G-to-A mutation frequencies induced by APOBEC3 proteins in H9 cells and peripheral blood mononuclear cells in the context of impaired processivities of drug-resistant human immunodeficiency virus type 1 reverse transcriptase variants. Journal of Virology, 82(13):6536-6545.

[img]
Preview
PDF
1MB

View at publisher

Abstract

APOBEC3 proteins can inhibit human immunodeficiency virus type 1 (HIV-1) replication by inducing G-to-A mutations in newly synthesized viral DNA. However, HIV-1 is able to overcome the antiretroviral activity of some of those enzymes by the viral protein Vif. We investigated the impact of different processivities of HIV-1 reverse transcriptases (RT) on the frequencies of G-to-A mutations introduced by APOBEC3 proteins. Wild-type RT or the M184V, M184I, and K65R+M184V RT variants, which are increasingly impaired in their processivities, were used in the context of a vif-deficient molecular HIV-1 clone to infect H9 cells and peripheral blood mononuclear cells (PBMCs). After two rounds of infection, a part of the HIV-1 env gene was amplified, cloned, and sequenced. The M184V mutation led to G-to-A mutation frequencies that were similar to those of the wild-type RT in H9 cells and PBMCs. The frequencies of G-to-A mutations were increased after infection with the M184I virus variant. This effect was augmented when using the K65R+M184V virus variant (P < 0.001). Overall, the G-to-A mutation frequencies were lower in PBMCs than in H9 cells. Remarkably, 38% +/- 18% (mean +/- standard deviation) of the env clones derived from PBMCs did not harbor any G-to-A mutation. This was rarely observed in H9 cells (3% +/- 3%). Our data imply that the frequency of G-to-A mutations induced by APOBEC3 proteins can be influenced by the processivities of HIV-1 RT variants. The high number of nonmutated clones derived from PBMCs leads to several hypotheses, including that additional antiretroviral mechanisms of APOBEC3 proteins other than their deamination activity might be involved in the inhibition of vif-deficient viruses.

Citations

9 citations in Web of Science®
9 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

77 downloads since deposited on 22 Dec 2008
35 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
DDC:610 Medicine & health
Language:English
Date:2008
Deposited On:22 Dec 2008 12:48
Last Modified:27 Nov 2013 18:37
Publisher:American Society for Microbiology
ISSN:0022-538X
Additional Information:Copyright: American Society for Microbiology
Publisher DOI:10.1128/JVI.00554-08
PubMed ID:18448538

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page