Abstract
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 0ΔNLS, achieved an optimal balance between avirulence and immunogenicity. HSV-2 0ΔNLS was interferon-sensitive in cultured cells. HSV-2 0ΔNLS 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 0ΔNLS failed to spread from sites of inoculation, and hence produced only inapparent infections. Mice inoculated with HSV-2 0ΔNLS 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.
Highlights
Herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2) may cause primary genital herpes [1,2,3]
We report that one HSV-2 ICP02 mutant virus in particular, HSV-2 0DNLS, exhibited such properties
We propose that interferon-sensitive HSV-2 ICP02 mutant viruses warrant consideration for their potential to prevent the spread of HSV-2 and genital herpes in the human population
Summary
Herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2) may cause primary genital herpes [1,2,3]. More than 90% of cases of recurrent genital herpes are caused by HSV-2 [1,4]. Recurrent genital herpes is a physically superficial disease in most cases, but often produces emotionally debilitating effects [5,6,7]. HSV-1 and HSV-2 establish life-long infections in their human hosts, and both viruses persist by establishing latent infections in the human nervous system. Infections with these viruses are exceedingly common; HSV-1 infects ,4 billion people and HSV-2 infects ,1 billion people [8]. 5% of HSV-2 infected individuals live with genital herpes disease that recurs once every 3 to 12 months [9,10]. An effective HSV-2 vaccine would be useful in breaking this cycle, and protecting young adults from the 1 in 10 chance that they will acquire HSV-2 before they marry [4,11,12]
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