Protease-deficient herpes simplex virus protects mice from lethal herpesvirus infection.
Null mutants and attenuated mutants of herpes simplex virus (HSV) have been shown to induce immunity against challenge from wild-type virus. Null viruses with a defect in late gene products would be expected to express more viral genes than viruses with defects in essential early gene products and thus induce a better immune response. Herpesviruses encode a late gene product (serine protease) that is autocatalytic and cleaves the capsid assembly protein during viral replication. To determine whether a virus with a mutation in this gene could induce immunity, we constructed a recombinant virus containing the gusA reporter gene in the protease domain of the HSV type 1 UL26 open reading frame (ORF). Consistent with previous results (M. Gao, L. Matusick-Kumar, W. Hurlburt, S. F. DiTusa, W. W. Newcomb, J. C. Brown, P. J. McCann, I. Deckman, and R. J. Colonno, J. Virol. 68:3702-3712, 1994), recombinant virus could be isolated only from helper cell lines expressing the product of the UL26 ORF. Mice inoculated with the recombinant virus were unaffected by doses of virus that were lethal to mice infected with wild-type virus. Mice which were previously inoculated with the recombinant virus were also protected by a subsequent challenge with wild-type virus in a dose-dependent manner. These results indicate that recombinant viruses lacking the protease gene are avirulent but render protection from subsequent challenge.
Hippenmeyer
P J
PJ
G.D. Searle, St. Louis, Missouri 63198, USA. pjhipp@ccmail.monsanto.com
Rankin
A M
AM
Luckow
V A
VA
Neises
G R
GR
D000818:Animals; D001483:Base Sequence; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000276:immunology*; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006566:Herpesviridae Infections / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008969:Molecular Sequence Data; D012697:Serine Endopeptidases / Q000235:genetics*; D018139:Simplexvirus / Q000235:genetics* / Q000276:immunology
D004274:DNA, Recombinant; D004279:DNA, Viral; D012697:Serine Endopeptidases