MIXED VAGINAL INFECTIONS OF BALB C MICE WITH LOW VIRULENT HERPES-SIMPLEX TYPE-1 STRAINS RESULT IN RESTORATION OF VIRULENCE PROPERTIES - VAGINITIS/VULVITIS AND NEUROINVASIVENESS/

Vaginal infections of BALB/c Ann mice with herpes simplex virus type 1 (HSV-1) were studied. Mice were inoculated with virulent strains ANG path and 17 syn(+) or low-virulent recombinant strains 27/III and 17-s yn3 that differ from parental strains in their glycoprotein B (gB) gen e sequences. When low-virulent strains were inoculated separately, no vaginitis/vulvitis was produced despite replication in the vagina. In contrast, after coinfection of mice with the two low-virulent strains, vaginitis/vulvitis was produced and virus could be recovered from the central nervous system (CNS). Two of the CNS isolates produced vagini tis/vulvitis, neuroinvasiveness and death of mice after vaginal infect ion. Restriction fragment analysis and sequencing were used to assess recombination events in the gB gene sequence of the CNS isolates. Afte r mixed vaginal infection recombination between non-virulent HSV strai ns occurs, resulting in vaginitis/vulvitis and neuroinvasiveness. No c orrelation was detected between the syncytial phenotype and local vagi nal virulence. Virulence of HSV is not solely dependent on gB function ; it seems to be more probable that several genes act in concert to in duce virulence and neuroivasiveness.