![]() ![]() The highly prevalent human herpes simplex viruses HSV-1 and HSV-2 are responsible for facial and genital herpes, potentially blinding eye infections, and life-threatening encephalitis and meningitis. Human and animal alphaherpesviruses establish lifelong latent infections in neurons of the peripheral nervous system and cause many diseases upon primary infection as well as following reactivation from latency. Our data indicate that capsid motility in the somata of neurons mediated by pU元6 and pU元7 does not suffice for targeting capsids to axons, and suggest that capsid envelopment needs to be completed in the soma prior to targeting of herpes simplex virus to the axons, and to spreading from neurons to neighboring cells. Employing a novel image analysis algorithm to quantify capsid targeting to axons, we show that only a few capsids of HSV1-ΔUL20 entered axons, while vesicles transporting gD utilized axonal transport efficiently and independently of pU元6, pU元7, or pUL20. While capsids of HSV1-ΔUL20 were actively transported along microtubules in epithelial cells and in the somata of neurons, those of HSV1-ΔU元6 and -ΔU元7 could only diffuse in the cytoplasm. ![]() Such neurons were infected with HSV1-ΔUL20 whose capsids recruited pU元6 and pU元7, with HSV1-ΔU元7 whose capsids associate only with pU元6, or with HSV1-ΔU元6 that assembles capsids lacking both proteins. We used HSV mutants impaired in capsid envelopment to test whether the inner tegument proteins pU元6 or pU元7 necessary for microtubule-mediated capsid transport were sufficient for axonal capsid targeting in neurons derived from the dorsal root ganglia of adult mice. It is debated whether capsid envelopment of herpes simplex virus (HSV) is completed in the soma prior to axonal targeting or later, and whether the mechanisms are the same in neurons derived from embryos or from adult hosts. Upon reactivation from latency and during lytic infections in neurons, alphaherpesviruses assemble cytosolic capsids, capsids associated with enveloping membranes, and transport vesicles harboring fully enveloped capsids. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |