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CO Ekworomadu, JY Ling, TM Chen, Y Cia, S Brown, S Lewis, RD Dix; Does the Gamma 34.5 Gene of HSV-1 Play a Role in HSV-1 Retinovirulence? . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4312.
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Purpose: To explore a possible role for gamma 34.5 gene function in the pathogenesis of experimental HSV-1 retinitis (von Szily model). HSV-1 is a recurrent herpesvirus that can invade the brain to cause a life-threatening encephalitis and/or invade the retina to cause a sight-threatening retinitis. Since neurovirulence of HSV-1 in mice has been mapped to the gamma 34.5 gene of the virus, we hypothesized that HSV-1 retinovirulence also requires gamma 34.5 gene function in both immunocompetent and immunosuppressed hosts. Methods: Groups of normal C57BL/6 mice or C57BL/6 mice with retrovirus-induced immunodeficiency syndrome (MAIDS) were infected with either the H129 strain (wild type) or the R52 strain (gamma 34.5 mutant) of HSV-1 by uniocular anterior chamber inoculation. All mice were assessed over time for development of clinical encephalitis, for development of retinitis in the inoculated (ipsilateral) and uninoculated (contralateral) eyes, and for the amount of infectious virus in ipsilteral eyes and brain halves. Results: Both immunocompetent and MAIDS mice inoculated with H129 developed clinical encephalitis, bilateral retinitis, and high titers of virus in the ipsilateral eye and adjacent brain half. In sharp contrast, both immunocompetent and MAIDS mice inoculated with R52 failed to develop clinical encephalitis or retinitis. Surprisingly, infectious virus was detected in the inoculated eye of all animals in the absence of retinitis. Conclusion: We conclude that the gamma 34.5 gene function is required for HSV-1 retinovirulence (retinitis) in the ipsilateral eye and for virus spread from the ipsilateral eye to the contralateral eye through the brain. Results were not influenced by the immune status of the host. Of significance, loss of the gamma 34.5 gene function still allowed for virus replication within the inoculated eye but without development of retinitis.
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