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.
Lewandowski
G
G
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hobbs
M
M
Geller
A
A
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000821:virology; D016923:Cell Death; D018792:Encephalitis, Viral / Q000503:physiopathology*; D006561:Herpes Simplex / Q000503:physiopathology*; D007371:Interferon-gamma / Q000172:deficiency* / Q000502:physiology; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D018139:Simplexvirus / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D014161:Transduction, Genetic; D014774:Virulence; D014779:Virus Replication
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D007371:Interferon-gamma