An in vivo study of a glycoprotein gIII-negative bovine herpesvirus 1 (BHV-1) mutant expressing beta-galactosidase: evaluation of the role of gIII in virus infectivity and its use as a vector for mucosal immunization.
We constructed a recombinant BHV-1 in which the glycoprotein gIII gene was replaced by the Escherichia coli lacZ gene. The resultant virus mimics the simple gIII deletion mutant in its growth characteristics in cell culture; however, it expresses beta-galactosidase in virus-infected cells. Further characterization of its virulence and the immune responses elicited by it was conducted in cattle. The mutant virus retained the ability to establish an infection when administered intranasally. Infected animals were also capable of transmitting virus to sentinel penmates. However, the mutant virus showed a reduced replication efficiency in the respiratory tract of cattle, as manifested by significantly lower virus shedding and a shorter duration of shedding when compared to wild-type (wt) BHV-1 infections. The mutant virus induced an efficient anti-BHV-1 antibody response and convalescent cattle were fully protected from subsequent wt virus challenge. In addition, cattle infected with the lacZ-expressing virus developed antibodies to beta-galactosidase. Our results demonstrate that the presence of gIII is not a prerequisite for BHV-1 infection; however, gIII does play an important role in maintaining virus replication efficacy in its natural host. With respect to developing BHV-1 as a vaccine vector, our results indicate that deletion of the gIII gene, which partially attenuates the virus and serves as a vaccine virus marker, does not compromise immunogenicity to BHV-1. Most importantly, this vector is effective in delivering foreign antigens to mucosal surfaces of the respiratory tract.
Liang
X
X
Veterinary Infectious Disease Organization, University of Saskatchewan, Saskatoon, Canada.
Babiuk
L A
LA
Zamb
T J
TJ
D000818:Animals; D000917:Antibody Formation; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D002872:Chromosome Deletion; D004274:DNA, Recombinant; D007242:Herpesvirus 1, Bovine / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D066298:In Vitro Techniques; D007241:Infectious Bovine Rhinotracheitis / Q000276:immunology / Q000382:microbiology* / Q000635:transmission; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000382:microbiology; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012137:Respiratory System / Q000382:microbiology*; D014764:Viral Proteins / Q000502:physiology*; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
D004274:DNA, Recombinant; D009838:Oligodeoxyribonucleotides; D014764:Viral Proteins; C046998:bovine herpesvirus type-1 glycoproteins; D001616:beta-Galactosidase