GENETIC AND FUNCTIONAL COMPLEMENTATION OF THE HSV1 UL27 GENE AND GB GLYCOPROTEIN BY SIMIAN ALPHA-HERPESVIRUS HOMOLOGS

Utilizing co-transfection of DNA from glycoprotein gB(-) strain of HSV 1 and cloned fragments of several simian alpha-herpesviruses containin g the UL26, UL27 (gB glycoprotein), and UL28 gene homologs, replicatio n-competent recombinant viruses were produced. Genetic analysis of one HSVI/SA8 recombinant (HSV1/SgB) demonstrated the presence of SA8 DNA comprising the entire UL27 (gB) gene and parts of the UL28 and UL26 OR Fs in an otherwise HSV1 genome. The recombinant was shown to express t he SA8 gB and p40 proteins (UL27 & UL26.5 gene products, respectively) ; all other proteins were indistinguishable from those of HSV1. The re combinant behaved like SA8 in gB-specific virus neutralization and cel l surface antibody binding assays, while plaque morphology and replica tion kinetics were very similar to HSV1. Despite its overwhelming HSV1 genetic constitution, the recombinant displayed a pathogenic phenotyp e in mice very different from the parental HSV1. While HSV1 produced c orneal disease in ocularly infected mice and readily spread to the ner vous system, HSV1/SgB was markedly impaired in both respects. These re sults demonstrate the functional equivalency of the cercopithecine mon key virus gB glycoproteins and genes (including transcriptional regula tory elements) in HSV1, the funtional nature of HSV1/SA8 chimeric UL28 and UL26 genes/proteins, and that UL28, gB and/or p40 proteins may ef fect the pathogenicity of HSV1.