Herpes simplex virus 2 ICP0 mutant viruses are avirulent and immunogenic: implications for a genital herpes vaccine.
Herpes simplex virus 1 (HSV-1) ICP0(-) mutants are interferon-sensitive, avirulent, and elicit protective immunity against HSV-1 (Virol J, 2006, 3:44). If an ICP0(-) mutant of herpes simplex virus 2 (HSV-2) exhibited similar properties, such a virus might be used to vaccinate against genital herpes. The current study was initiated to explore this possibility. Several HSV-2 ICP0(-) mutant viruses were constructed and evaluated in terms of three parameters: i. interferon-sensitivity; ii. virulence in mice; and iii. capacity to elicit protective immunity against HSV-2. One ICP0(-) mutant virus in particular, HSV-2 0DeltaNLS, achieved an optimal balance between avirulence and immunogenicity. HSV-2 0DeltaNLS was interferon-sensitive in cultured cells. HSV-2 0DeltaNLS replicated to low levels in the eyes of inoculated mice, but was rapidly repressed by an innate, Stat 1-dependent host immune response. HSV-2 0DeltaNLS failed to spread from sites of inoculation, and hence produced only inapparent infections. Mice inoculated with HSV-2 0DeltaNLS consistently mounted an HSV-specific IgG antibody response, and were consistently protected against lethal challenge with wild-type HSV-2. Based on their avirulence and immunogenicity, we propose that HSV-2 ICP0(-) mutant viruses merit consideration for their potential to prevent the spread of HSV-2 and genital herpes.
Halford
William P
WP
Department of Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois, United States of America. halford@siumed.edu
Püschel
Ringo
R
Rakowski
Brandon
B
D000818:Animals; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D007121:Immunocompetence; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D050794:STAT1 Transcription Factor / Q000378:metabolism; D012449:Safety; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000009:adverse effects / Q000235:genetics* / Q000276:immunology*
D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D016899:Interferon-beta; D044767:Ubiquitin-Protein Ligases
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