Role of kinesins in directed adenovirus transport and cytoplasmic exploration

PLoS Pathogens
Jie ZhouRichard B Vallee

Abstract

Many viruses, including adenovirus, exhibit bidirectional transport along microtubules following cell entry. Cytoplasmic dynein is responsible for microtubule minus end transport of adenovirus capsids after endosomal escape. However, the identity and roles of the opposing plus end-directed motor(s) remain unknown. We performed an RNAi screen of 38 kinesins, which implicated Kif5B (kinesin-1 family) and additional minor kinesins in adenovirus 5 (Ad5) capsid translocation. Kif5B RNAi markedly increased centrosome accumulation of incoming Ad5 capsids in human A549 pulmonary epithelial cells within the first 30 min post infection, an effect dramatically enhanced by blocking Ad5 nuclear pore targeting using leptomycin B. The Kif5B RNAi phenotype was rescued by expression of RNAi-resistant Kif5A, B, or C, and Kif4A. Kif5B RNAi also inhibited a novel form of microtubule-based "assisted-diffusion" behavior which was apparent between 30 and 60 min p.i. We found the major capsid protein penton base (PB) to recruit kinesin-1, distinct from the hexon role we previously identified for cytoplasmic dynein binding. We propose that adenovirus uses independently recruited kinesin and dynein for directed transport and for a more random microtubul...Continue Reading

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Citations

Jul 10, 2019·Annual Review of Virology·Urs F Greber, Justin W Flatt
Nov 24, 2019·FEBS Letters·Noémie Pied, Harald Wodrich
Mar 28, 2020·FEBS Letters·Julian SchererRichard B Vallee
Aug 9, 2020·Frontiers in Molecular Neuroscience·Andrew P Tosolini, James N Sleigh
Jun 17, 2020·FEBS Letters·Urs F Greber
Dec 18, 2020·Frontiers in Cellular and Infection Microbiology·Kuldeep Sachdeva, Varadharajan Sundaramurthy

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Methods Mentioned

BETA
co-immunoprecipitation
size exclusion chromatography
pull-down
immunoprecipitation
pull-downs
PCR
transfections
immunoprecipitations

Software Mentioned

MATLAB
Excel
R

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