Cytoplasmic dynein promotes HIV-1 uncoating.
Retroviral capsid (CA) cores undergo uncoating during their retrograde transport (toward the nucleus), and/or after reaching the nuclear membrane. However, whether HIV-1 CA core uncoating is dependent upon its transport is not understood. There is some evidence that HIV-1 cores retrograde transport involves cytoplasmic dynein complexes translocating on microtubules. Here we investigate the role of dynein-dependent transport in HIV-1 uncoating. To interfere with dynein function, we depleted dynein heavy chain (DHC) using RNA interference, and we over-expressed p50/dynamitin. In immunofluorescence microscopy experiments, DHC depletion caused an accumulation of CA foci in HIV-1 infected cells. Using a biochemical assay to monitor HIV-1 CA core disassembly in infected cells, we observed an increase in amounts of intact (pelletable) CA cores upon DHC depletion or p50 over-expression. Results from these two complementary assays suggest that inhibiting dynein-mediated transport interferes with HIV-1 uncoating in infected cells, indicating the existence of a functional link between HIV-1 transport and uncoating.
Laboratory of Retrovirology, Department of Medical Biology and BioMed Research Center, Université du Québec à Trois-Rivières, 3351 Boulevard des Forges, Trois-Rivières, QC G9A 5H7, Canada. paulina.pawlica@uqtr.ca.
Paulina
P
Pawlica
Laboratory of Retrovirology, Department of Medical Biology and BioMed Research Center, Université du Québec à Trois-Rivières, 3351 Boulevard des Forges, Trois-Rivières, QC G9A 5H7, Canada. berthoux@uqtr.ca.
Lionel
L
Berthoux
D001692:Biological Transport; D002213:Capsid / Q000378:metabolism; D056445:Cytoplasmic Dyneins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D057646:Virus Uncoating
D056445:Cytoplasmic Dyneins