The role of the UL41 gene of herpes simplex virus type 1 in evasion of non-specific host defence mechanisms during primary infection

The UL41 gene product (vhs) of herpes simplex virus (HSV) is packaged in th e virion, and mediates host protein synthesis shutoff at the early stage of the virus replication cycle, In order to clarify the role of vhs in virus replication and virulence, we isolated a completely UL41-deficient mutant ( the VR Delta 41 strain) and its revertant (the VR Delta 41R strain), In the mouse encephalitis model, the replication of strain VR Delta 41 was inhibi ted after 2 days post-infection, resulting in low virulence, by gamma-ray-s ensitive cells such as lymphocytes and/or neutrophils, The result suggested that some cytokines, produced in VR Delta 41-inoculated brains, activate a nd induce the migration of gamma-ray-sensitive cells to the infection site. Therefore, cytokines produced by HSV-l-infected human cells were screened, and potent inductions of interleukin (IL)-1 beta, IL-8 and macrophage infl ammatory protein-1 alpha by VR Delta 41 infection were observed, Moreover, the VR Delta 41 strain showed 20- and 5-fold higher sensitivity to interfer on-alpha and -beta compared to the wild-type strain, respectively. These re sults indicate that one important role of vhs in vivo is evasion from non-s pecific host defence mechanisms during primary infection through suppressio n of cytokine production in HSV-infected cells and reduction of the anti-HS V activity of interferon-alpha and -beta.