Intertypic superinfection of herpes simplex virus in vivo leads to reisolation of latent viruses with newly acquired lymphotropic properties.

The susceptibility of juvenile Tupaias to several strains of temperature-sensitive mutants of HSV-1 and 2 was tested. It was found that in all cases the animal survived an infection of 1 X 10(7) PFU of temperature-sensitive mutants which were administered intravenously. In contrast, an infection dose of 1 X 10(3) PFU of wild-type HSV-2 and 1 X 10(2) PFU or HSV-1 was fatal for juvenile Tupaias. Those animals which had initially been infected with the ts-mutants of HSV-1 and/or 2 were protected against a superinfection of a lethal dose of HSV-1 or HSV-2. The state of HSV latency in surviving animals was investigated. The infectious virus was recovered from the spinal cords of those animals which had been initially infected with wild-type HSV-1 or 2 and/or superinfected with HSV-1 or 2. In contrast, the infectious viruses were recovered only from the spleens of those animals which had initially been infected with ts-mutants of HSV-2 and superinfected with HSV-1. These recovered viruses were plaque-purified and analysed in detail. It was found, firstly, that recovered viruses from the spleens of Tupaias lost their pathogenicity and tropism in Tupaias. Secondly, significant changes in the genome of the recovered viruses from the spleen of Tupaias were detected. The results indicate that an intertypic interaction between HSV-1 and 2 occurred in vivo which is responsible for the observed change in organotropism and pathogenicity of the recovered viruses.