Guanylate Binding Protein (GBP) 5 Is an Interferon-Inducible Inhibitor of HIV-1 Infectivity.

Details

Serval ID
serval:BIB_A84717BFC1B2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Guanylate Binding Protein (GBP) 5 Is an Interferon-Inducible Inhibitor of HIV-1 Infectivity.
Journal
Cell Host and Microbe
Author(s)
Krapp C., Hotter D., Gawanbacht A., McLaren P.J., Kluge S.F., Stürzel C.M., Mack K., Reith E., Engelhart S., Ciuffi A., Hornung V., Sauter D., Telenti A., Kirchhoff F.
ISSN
1934-6069 (Electronic)
ISSN-L
1931-3128
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
19
Number
4
Pages
504-514
Language
english
Abstract
Guanylate binding proteins (GBPs) are an interferon (IFN)-inducible subfamily of guanosine triphosphatases (GTPases) with well-established activity against intracellular bacteria and parasites. Here we show that GBP5 potently restricts HIV-1 and other retroviruses. GBP5 is expressed in the primary target cells of HIV-1, where it impairs viral infectivity by interfering with the processing and virion incorporation of the viral envelope glycoprotein (Env). GBP5 levels in macrophages determine and inversely correlate with infectious HIV-1 yield over several orders of magnitude, which may explain the high donor variability in macrophage susceptibility to HIV. Antiviral activity requires Golgi localization of GBP5, but not its GTPase activity. Start codon mutations in the accessory vpu gene from macrophage-tropic HIV-1 strains conferred partial resistance to GBP5 inhibition by increasing Env expression. Our results identify GBP5 as an antiviral effector of the IFN response and may explain the increased frequency of defective vpu genes in primary HIV-1 strains.
Pubmed
Web of science
Open Access
Yes
Create date
16/02/2016 18:48
Last modification date
20/08/2019 16:12
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