Human immunodeficiency virus type 1 Vif functionally interacts with diverse APOBEC3 cytidine deaminases and moves with them between cytoplasmic sites of mRNA metabolism

Mariana Marin, Sheetal Golem, Kristine M. Rose, Susan L. Kozak, David Kabat

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

VifIIIB, which has been a standard model for the viral infectivity factor of human immunodeficiency virus type 1 (HIV-1), binds the cytidine deaminase APOBEC3G (A3G) and induces its degradation, thereby precluding its lethal incorporation into assembling virions. Additionally, YifIIIB less efficiently degrades A3F, another potent anti-HIV-1 cytidine deaminase. Although the APOBEC3 paralogs A3A, A3B, and A3C have weaker anti-HIV-1 activities and are only partially degraded by VifIIIB, we found that VifIIIB induces their emigration from the nucleus to the cytosol and thereby causes net increases in the cytosolic concentrations and anti-HIV-1 activities of A3A and A3B. In contrast, some other Vifs, exemplified by VifHXB2 and VifELI-1, much more efficiently degrade and thereby neutralize all APOBEC3s. Studies focused mainly on A3F imply that it occurs associated with mRNA-PABP1 in translationally active polysomes and to a lesser extent in mRNA processing bodies (P-bodies). A3F appears to stabilize the P-bodies with which it is associated. A correspondingly small proportion of VifIIIB also localizes in P-bodies in an A3F-dependent manner. Stress causes A3A, A3B, A3C, and A3F to colocalize efficiently with VifIIIB and mRNA-PABP1 complexes in stress granules in a manner that is prevented by cycloheximide, an inhibitor of translational elongation. Coimmunoprecipitation studies suggest that Vifs from different HIV-1 isolates associate with all tested APOBEC3s. Thus, Vifs interact closely with structurally diverse APOBEC3s, with effects on their subcellular localization, degradation rates, and antiviral activities. Cytosolic APOBEC3-Vif complexes are predominantly bound to mRNAs that dynamically move between translationally active and storage or processing pools.

Original languageEnglish (US)
Pages (from-to)987-998
Number of pages12
JournalJournal of Virology
Volume82
Issue number2
DOIs
StatePublished - Jan 2008

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Cytidine Deaminase
Human immunodeficiency virus 1
HIV-1
Messenger RNA
metabolism
polyribosomes
Polyribosomes
degradation
Emigration and Immigration
cycloheximide
Cycloheximide
virion
cytosol
Virion
Cytosol
Antiviral Agents
granules
pathogenicity
cytidine deaminase

ASJC Scopus subject areas

  • Immunology

Cite this

Human immunodeficiency virus type 1 Vif functionally interacts with diverse APOBEC3 cytidine deaminases and moves with them between cytoplasmic sites of mRNA metabolism. / Marin, Mariana; Golem, Sheetal; Rose, Kristine M.; Kozak, Susan L.; Kabat, David.

In: Journal of Virology, Vol. 82, No. 2, 01.2008, p. 987-998.

Research output: Contribution to journalArticle

Marin, Mariana ; Golem, Sheetal ; Rose, Kristine M. ; Kozak, Susan L. ; Kabat, David. / Human immunodeficiency virus type 1 Vif functionally interacts with diverse APOBEC3 cytidine deaminases and moves with them between cytoplasmic sites of mRNA metabolism. In: Journal of Virology. 2008 ; Vol. 82, No. 2. pp. 987-998.
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