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 HSV1 and cloned fragments of several simian alpha-herpesviruses containing the UL26, UL27 (gB glycoprotein), and UL28 gene homologs, replication-competent recombinant viruses were produced. Genetic analysis of one HSV1/SA8 recombinant (HSV1/SgB) demonstrated the presence of SA8 DNA comprising the entire UL27 (gB) gene and parts of the UL28 and UL26 ORFs in an otherwise HSV1 genome. The recombinant was shown to express the SA8 gB and p40 proteins (UL27 & UL26.5 gene products, respectively); all other proteins were indistinguishable from those of HSV1. The recombinant behaved like SA8 in gB-specific virus neutralization and cell surface antibody binding assays, while plaque morphology and replication kinetics were very similar to HSV1. Despite its overwhelming HSV1 genetic constitution, the recombinant displayed a pathogenic phenotype in mice very different from the parental HSV1. While HSV1 produced corneal disease in ocularly infected mice and readily spread to the nervous system. HSV1/SgB was markedly impaired in both respects. These results demonstrate the functional equivalency of the cercopithecine monkey virus gB glycoproteins and genes (including transcriptional regulatory elements) in HSV1, the functional nature of HSV1/SA8 chimeric UL28 and UL26 genes/proteins, and that UL28, gB and/or p40 proteins may effect the pathogenicity of HSV1.
Eberle
R
R
Department of Infectious Diseases and Physiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, USA.
Tanamachi
B
B
Black
D
D
Blewett
E L
EL
Ali
M
M
Openshaw
H
H
Cantin
E M
EM
D016475:3T3 Cells; D000818:Animals; D002522:Chlorocebus aethiops; D005816:Genetic Complementation Test; D016679:Genome, Viral; D006568:Herpesvirus 1, Cercopithecine / Q000235:genetics* / Q000502:physiology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D051379:Mice; D011995:Recombination, Genetic; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics*; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000235:genetics
D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus