|Dean hansi j,|
Submitted to: Virology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/31/1996
Publication Date: N/A
Citation: Interpretive Summary: Pseudorabies virus (PRV) causes a contagious and sometimes fatal disease of swine, which results in significant economic losses to the U.S. swine industry. PRV is a neurotropic virus which spreads to and infects the central nervous system of susceptible animals. Previously, we genetically engineered a strain of PRV which was deleted for a portion of the viral genome. The recombinant virus was reduced in virulence, with respect to ability to cause neurological disease and death in pigs. To determine the basis for the reduced virulence, pigs were infected with recombinant or control virus, and tissues were examined at various times after infection. The results indicated that the recombinant virus was specifically reduced in ability to replicate in and destroy cells of the central nervous system, while its properties were not affected in other tissues.
Technical Abstract: Pseudorabies virus (PRV) is a neurotropic herpesvirus of swine. Previously, we described construction of a recombinant strain of PRV (LLTBD2) which contains a 3.0 kb deletion spanning the junction of the unique long and internal repeat sequences. Compared to the parental strain, Indiana-Funkhauser, and a virus rescued for the deleted sequences (LLTBres), LLTBD2 replicated efficiently at the site of inoculation, yet exhibited significantly reduced virulence when inoculated intranasally in pigs. In particular, the LLTBD2-infected pigs did not exhibit neurological signs characteristic of PRV infection. To localize the defect in LLTBD2, 4-day-old-pigs were infected intranasally with LLTBD2 or LLTBres and necropsied at various times postinfection. Tissue distribution of virus, PRV antigen, and lesions were compared between the two strains. LLTBD2 was not impaired in replication in trigeminal ganglia or other peripheral tissues, and was neuroinvasive (spread to the central nervous system (CNS), but was restricted in replication in the CNS. These results indicate that sequences at the UL/IR junction contain a determinant of PRV neurovirulence (ability to replicate in CNS and cause neurological signs) which is specifically required for replication in the CNS, and not peripheral tissues or TG of the natural host animal. B=beta, D=delta