The gamma(1)34.5 gene of herpes simplex virus is dispensable in some cell lines (e.g., Vero). This finding could lead the way to the creation of anti-viral drugs based on non-psychoactive derivatives of THC. HSV can also progress to active lytic replication in the central nervous system, resulting in devastating encephalitis. We have found that like HSV-1, IFN-gamma synergizes with IFN-alpha to inhibit HSV-2 replication in Vero cells. Considerable sequence differences (amino acid identities: 49-89%) were found between the novel virus and PLHV-1 as well as PLHV-2, which were very closely related to each other (amino acid identities: 85-98%). This engineered vector (dvHSV/MulFN-gamma) inhibited the proliferation of mouse glioma RSV cells in vitro, and an intratumoral (i.t.) local injection of the vector caused i.t. To gain more insight into the role of IFN gamma, anti-IFN gamma monoclonal antibodies were added to PBMC stimulated with LPS.
However, the pattern of IFN-gamma production by CD4(+) and CD8(+) T cells differed according to the recombinant virus used. Furthermore, addition of IFN-gamma resulted in enhanced HSV replication in monocytic cells of HSV-infected individuals with recurrent disease, in contrast to the inhibition observed in HSV-seropositive asymptomatic individuals and seronegative controls. Mice immunized with IL-4-expressing virus cleared the virus from their eyes more rapidly than mice immunized with IL-2- or IFN-gamma-expressing virus. Taken together, our results suggest that, in contrast to IFN-gamma which did not exhibit an adjuvant effect, both IL-4 and IL-2 act as adjuvants in immunization with HSV, with IL-4 showing greater efficacy.