Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores.

Abstract:

:We previously showed that reduced infectivity of HIV with incompletely processed capsid-spacer protein 1 (CA-SP1) is rescued by cellular activation or increased expression of HSP90AB1, a member of the cytosolic heat shock protein 90 family. Here we show that HSP90AB1 is present in HIV virions and that HSP90AB1, but not nonfunctional mutated HSP90AB1(E42A+D88A), restores infectivity to HIV with mutations in CA that alter core stability. Further, the CA mutants were hypersensitive to pharmacological inhibition of HSP90AB1. In agreement with Roesch et al. (2012), we found that culturing HIV at 39.5°C enhanced viral infectivity up to 30-fold in human peripheral blood mononuclear cells (p=0.002) and rescued CA-mutant infectivity in nonactivated cells, concurrent with elevated expression of HSP90AB1 during hyperthermia. In sum, the transdominant effect of HSP90AB1 on CA-mutant HIV infectivity suggests a potential role for this class of cellular chaperones in HIV core stability and uncoating.

journal_name

Virology

journal_title

Virology

authors

Joshi P,Sloan B,Torbett BE,Stoddart CA

doi

10.1016/j.virol.2012.11.005

subject

Has Abstract

pub_date

2013-02-05 00:00:00

pages

162-72

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(12)00552-1

journal_volume

436

pub_type

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