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.
Item Type: | Journal article |
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Faculties: | Chemistry and Pharmacy > Department of Biochemistry |
Subjects: | 500 Science > 540 Chemistry |
ISSN: | 1931-3128 |
Language: | English |
Item ID: | 48524 |
Date Deposited: | 27. Apr 2018, 08:15 |
Last Modified: | 04. Nov 2020, 13:26 |