TY - JOUR
T1 - Herpes simplex virus gE/gI and US9 proteins promote transport of both capsids and virion glycoproteins in neuronal axons
AU - Snyder, Aleksandra
AU - Polcicova, Katarina
AU - Johnson, David C.
PY - 2008/11
Y1 - 2008/11
N2 - Following reactivation from latency, alphaherpesviruses replicate in sensory neurons and assemble capsids that are transported in the anterograde direction toward axon termini for spread to epithelial tissues. Two models currently describe this transport. The Separate model suggests that capsids are transported in axons independently from viral envelope glycoproteins. The Married model holds that fully assembled enveloped virions are transported in axons. The herpes simplex virus (HSV) membrane glycoprotein heterodimer gE/gI and the US9 protein are important for virus anterograde spread in the nervous systems of animal models. It was not clear whether gE/gI and US9 contribute to the axonal transport of HSV capsids, the transport of membrane proteins, or both. Here, we report that the efficient axonal transport of HSV requires both gE/gI and US9. The transport of both capsids and glycoproteins was dramatically reduced, especially in more distal regions of axons, with gE-, gI-, and US9-null mutants. An HSV mutant lacking just the gE cytoplasmic (CT) domain displayed an intermediate reduction in capsid and glycoprotein transport. We concluded that HSV gE/gI and US9 promote the separate transport of both capsids and glycoproteins. gE/gI was transported in association with other HSV glycoproteins, gB and gD, but not with capsids. In contrast, US9 colocalized with capsids and not with membrane glycoproteins. Our observations suggest that gE/gI and US9 function in the neuron cell body to promote the loading of capsids and glycoprotein-containing vesicles onto microtubule motors that ferry HSV structural components toward axon tips.
AB - Following reactivation from latency, alphaherpesviruses replicate in sensory neurons and assemble capsids that are transported in the anterograde direction toward axon termini for spread to epithelial tissues. Two models currently describe this transport. The Separate model suggests that capsids are transported in axons independently from viral envelope glycoproteins. The Married model holds that fully assembled enveloped virions are transported in axons. The herpes simplex virus (HSV) membrane glycoprotein heterodimer gE/gI and the US9 protein are important for virus anterograde spread in the nervous systems of animal models. It was not clear whether gE/gI and US9 contribute to the axonal transport of HSV capsids, the transport of membrane proteins, or both. Here, we report that the efficient axonal transport of HSV requires both gE/gI and US9. The transport of both capsids and glycoproteins was dramatically reduced, especially in more distal regions of axons, with gE-, gI-, and US9-null mutants. An HSV mutant lacking just the gE cytoplasmic (CT) domain displayed an intermediate reduction in capsid and glycoprotein transport. We concluded that HSV gE/gI and US9 promote the separate transport of both capsids and glycoproteins. gE/gI was transported in association with other HSV glycoproteins, gB and gD, but not with capsids. In contrast, US9 colocalized with capsids and not with membrane glycoproteins. Our observations suggest that gE/gI and US9 function in the neuron cell body to promote the loading of capsids and glycoprotein-containing vesicles onto microtubule motors that ferry HSV structural components toward axon tips.
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U2 - 10.1128/JVI.01241-08
DO - 10.1128/JVI.01241-08
M3 - Article
C2 - 18753205
AN - SCOPUS:55249103906
SN - 0022-538X
VL - 82
SP - 10613
EP - 10624
JO - Journal of virology
JF - Journal of virology
IS - 21
ER -