TY - JOUR
T1 - The herpesvirus VP1/2 protein is an effector of dynein-mediated capsid transport and neuroinvasion
AU - Zaichick, Sofia V.
AU - Bohannon, Kevin P.
AU - Hughes, Ami
AU - Sollars, Patricia J.
AU - Pickard, Gary E.
AU - Smith, Gregory A.
N1 - Funding Information:
We thank Jenifer Klabis and Gina Daniel for producing recombinants of PRV used in these studies; Anna Akhmanova for constructs used in the mitochondrial experiments; and Duncan Wilson, Chris Wiethoff, and Mark Mandel for insightful discussions and suggestions. This work was funded by NIH grant R01 AI056346 to G.A.S. and R01 EY017809 to G.E.P. and P.J.S. K.P.B. received support from the training program in Immunology and Molecular Pathogenesis from the National Institutes of Health (T32AI07476).
PY - 2013/2/13
Y1 - 2013/2/13
N2 - Microtubule transport of herpesvirus capsids from the cell periphery to the nucleus is imperative for viral replication and, in the case of many alphaherpesviruses, transmission into the nervous system. Using the neuroinvasive herpesvirus, pseudorabies virus (PRV), we show that the viral protein 1/2 (VP1/2) tegument protein associates with the dynein/dynactin microtubule motor complex and promotes retrograde microtubule transport of PRV capsids. Functional activation of VP1/2 requires binding to the capsid protein pUL25 or removal of the capsid-binding domain. A proline-rich sequence within VP1/2 is required for the efficient interaction with the dynein/dynactin microtubule motor complex as well as for PRV virulence and retrograde axon transport in vivo. Additionally, in the absence of infection, functionally active VP1/2 is sufficient to move large surrogate cargoes via the dynein/dynactin microtubule motor complex. Thus, VP1/2 tethers PRV capsids to dynein/dynactin to enhance microtubule transport, neuroinvasion, and pathogenesis.
AB - Microtubule transport of herpesvirus capsids from the cell periphery to the nucleus is imperative for viral replication and, in the case of many alphaherpesviruses, transmission into the nervous system. Using the neuroinvasive herpesvirus, pseudorabies virus (PRV), we show that the viral protein 1/2 (VP1/2) tegument protein associates with the dynein/dynactin microtubule motor complex and promotes retrograde microtubule transport of PRV capsids. Functional activation of VP1/2 requires binding to the capsid protein pUL25 or removal of the capsid-binding domain. A proline-rich sequence within VP1/2 is required for the efficient interaction with the dynein/dynactin microtubule motor complex as well as for PRV virulence and retrograde axon transport in vivo. Additionally, in the absence of infection, functionally active VP1/2 is sufficient to move large surrogate cargoes via the dynein/dynactin microtubule motor complex. Thus, VP1/2 tethers PRV capsids to dynein/dynactin to enhance microtubule transport, neuroinvasion, and pathogenesis.
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U2 - 10.1016/j.chom.2013.01.009
DO - 10.1016/j.chom.2013.01.009
M3 - Article
C2 - 23414759
AN - SCOPUS:84873933638
VL - 13
SP - 193
EP - 203
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 2
ER -