The envelope gene of transmitted HIV-1 resists a late interferon gamma-induced block

Rihn, S. J. , Foster, T. L., Busnadiego, I., Aziz, M. A., Hughes, J. , Neil, S. J.D. and Wilson, S. J. (2017) The envelope gene of transmitted HIV-1 resists a late interferon gamma-induced block. Journal of Virology, 91(7), e02254-16. (doi:10.1128/JVI.02254-16) (PMID:28100611) (PMCID:PMC5355616)

[img]
Preview
Text
133882.pdf - Published Version
Available under License Creative Commons Attribution.

6MB

Abstract

Type I interferon (IFN) signaling engenders an antiviral state that likely plays an important role in constraining HIV-1 transmission and contributes to defining subsequent AIDS pathogenesis. Type II IFN (IFNγ) also induces an antiviral state but is often primarily considered to be an immunomodulatory cytokine. We report that IFNγ stimulation can induce an antiviral state that can be both distinct from that of type I interferon, and can potently inhibit HIV-1 in primary CD4+ T cells and a number of human cell lines. Strikingly, we find that transmitted/founder (TF) HIV-1 viruses can resist a late block that is induced by type II IFN, and the use of chimeric IFNγ- sensitive/resistant viruses indicates that interferon-resistance maps to the env gene. Simultaneously, in vitro evolution also revealed that just a single amino acid substitution in envelope can confer substantial resistance to IFN-mediated inhibition. Thus, the env gene of transmitted HIV-1 confers resistance to a late block that is phenotypically distinct from those previously described to be resisted by env, and is therefore mediated by unknown IFNγ-stimulated factor(s) in human CD4+ T cells and cell lines. This important unidentified block could play a key role in constraining HIV-1 transmission.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rihn, Dr Suzannah and Wilson, Dr Sam and Hughes, Dr Joseph and Busnadiego, Dr Idoia
Authors: Rihn, S. J., Foster, T. L., Busnadiego, I., Aziz, M. A., Hughes, J., Neil, S. J.D., and Wilson, S. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN:0022-538X
ISSN (Online):1098-5514
Published Online:18 January 2017
Copyright Holders:Copyright © 2017 Rihn et al.
First Published:First published in Journal of Virology 91(7):e02254-16
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
618831Identifying and characterising antiretroviral interferon stimulated genes (ISGs)Sam WilsonMedical Research Council (MRC)MR/K024752/1MVLS III - CENTRE FOR VIRUS RESEARCH