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J. H. LaVail, J. M. Draper; The HSV Protein VP22 Plays a Role in the Efficient Encephalitic Spread of Viral Capsid and DNA in vivo. Invest. Ophthalmol. Vis. Sci. 2009;50(13):841.
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© ARVO (1962-2015); The Authors (2016-present)
Herpes simplex virus (HSV) infections are responsible for recurrent herpetic keratitis, as well as sporadic acute encephalitis. Our goal is to identify the viral proteins that promote the spread of HSV in the nervous system. We have found that newly synthesized HSV is axonally transported in the anterograde direction in at least two sub-assemblies, one of which is composed of the viral capsid and DNA (nucleocapsid). We have also found that the protein, Us9, is essential for the transport of the nucleocapsid subassembly. In searching for other viral proteins that are required for efficient transport of the viral nucleocapsid, we found that mutant viral strains lacking VP22 expression do not deliver HSV DNA to the axon compartment. Furthermore, in wild type infected cells, the VP22 protein co-immunoprecipitates with antibodies to Us9. This suggested that VP22 and Us9 cooperate in the regulation of HSV DNA transport to and within the axon. We now test the hypothesis that VP22 protein is associated with Us9 in infected axons and is required for efficient anterograde transport of viral capsid, as defined by VP5 transport.
Murine retinal ganglion cells were infected with wild type, VP22-null or VP22-rescued viral strains. The anterograde transport of viral capsid and envelope proteins were assayed 5 days postinfection by Western blotting homogenates of axons of the optic nerve, optic chiasm and optic tract. We immunoprecipitated proteins that had affinity for Us9 in the axons and assayed for the presence of VP22 with mass spectrometry.
VP22 is necessary for the transport of viral DNA in retinal ganglion cell axons. Viral DNA was detected in the optic tract of VP22-rescued infected mice at 3 days postinfection, but could not be detected in the VP22-null infected mice. VP22 is also required for efficient transport of VP5. Preliminary studies indicate that there was also no detectable reduction in anterograde transport of gD, a major envelope protein, after infection with the VP22-null strain.
These results support the model of subassembly transport of viral components. We confirm that VP22 plays a role in the transport of the nucleocapid subassembly. We suggest that neither Us9 nor VP22 is essential for the transport of viral envelope proteins. The nucleocapsid is likely enveloped and released at sites along the axon as well as at synaptic endings. Lastly, we suggest that the two viral proteins are potential targets for pharmaceutical intervention.
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