Evidence that deficient IFN-gamma production is a biological basis of herpes simplex virus type-2 neurovirulence.

Although immune response control of herpes simplex virus (HSV) has been well demonstrated, numerous HSV-2 strains are neurovirulent in immunocompetent mice. Using an RNase protection assay and an ELISA, we found that HSV-2-infected mice exhibited a deficient IFN-gamma response, an inability to clear virus, and eventual death. An HSV-based amplicon vector expressing mouse IFN-gamma was constructed and packaged into HSV-1-helper virus (HSV(pIFN-gamma)). In mice treated with HSV(pIFN-gamma), (i) the LD50 of HSV-2(G) increased 5000-fold, (ii) intracerebral IFN-gamma expression increased 10-fold, and (iii) HSV titer rapidly decreased. We suggest that the deficient IFN-gamma response is a basis for HSV-2 neurovirulence in mice.