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Proc Natl Acad Sci U S A. 2017 Aug 15;114(33):E6932-E6941. doi: 10.1073/pnas.1700247114. Epub 2017 Jul 31.

Distinct functions of diaphanous-related formins regulate HIV-1 uncoating and transport.

Author information

1
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.
2
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 mojgan.naghavi@northwestern.edu.

Abstract

Diaphanous (Dia)-related formins (DRFs) coordinate cytoskeletal remodeling by controlling actin nucleation and microtubule (MT) stabilization to facilitate processes such as cell polarization and migration; yet the full extent of their activities remains unknown. Here, we uncover two discrete roles and functions of DRFs during early human immunodeficiency virus type 1 (HIV-1) infection. Independent of their actin regulatory activities, Dia1 and Dia2 facilitated HIV-1-induced MT stabilization and the intracellular motility of virus particles. However, DRFs also bound in vitro assembled capsid-nucleocapsid complexes and promoted the disassembly of HIV-1 capsid (CA) shell. This process, also known as "uncoating," is among the most poorly understood stages in the viral lifecycle. Domain analysis and structure modeling revealed that regions of Dia2 that bound viral CA and mediated uncoating as well as early infection contained coiled-coil domains, and that these activities were genetically separable from effects on MT stabilization. Our findings reveal that HIV-1 exploits discrete functions of DRFs to coordinate critical steps in early infection and identifies Dia family members as regulators of the poorly understood process of HIV-1 uncoating.

KEYWORDS:

HIV-1; HIV-1 uncoating; diaphanous-related formin; stable microtubules; viral trafficking

PMID:
28760985
PMCID:
PMC5565409
DOI:
10.1073/pnas.1700247114
[Indexed for MEDLINE]
Free PMC Article

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