Replication and pathogenicity after intranasal and intracranial inoculation of swine with a recombinant pseudorabies virus containing a deletion at the UL/IR junction.
Pseudorabies virus (PRV) is a neurotropic herpesvirus of swine. Previously, we described construction of a recombinant strain of PRV (LLT beta delta 2) 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 (LLT beta res), LLT beta delta 2 replicated efficiently at the site of inoculation, yet exhibited significantly reduced virulence when inoculated intranasally in pigs. In this report, we investigated the effect of the deletion on PRV replication and virulence after intracranial inoculation of swine, in comparison to replication and virulence after intranasal inoculation, in order to more precisely locate the defect in LLT beta delta 2. Four-day-old pigs were infected intranasally with LLT beta delta 2 or LLT beta res and necropsied at various times postinfection. Compared to LLT beta res-infected pigs, tissue distribution of virus, PRV antigen, and lesions of LLT beta delta 2-infected pigs were comparable in all peripheral tissues examined, including trigeminal ganglia, but were reduced in tissues from the central nervous system (CNS). LLT beta delta 2 was able to replicate in the CNS after intracranial inoculation into the cerebral cortex of 2-day-old piglets and to spread from CNS to peripheral tissues. Neurovirulence of LLT beta delta 2 was somewhat reduced, as demonstrated by delayed onset of neurological signs and death in intracranially inoculated pigs. These results indicate that decreased neurovirulence after intranasal inoculation is not due to inability of LLT beta delta 2 to replicate in CNS tissues. The difference in the amount of antigen detected in CNS tissues after intracranial inoculation compared to intranasal inoculation suggests that one defect in LLT beta delta 2 is reduced ability to spread from peripheral neurons to the CNS after intranasal inoculation.
Dean
H J
HJ
Virology Swine, Disease Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa 50010, USA.
Miller
J M
JM
Ackermann
M R
MR
Gao
X Y
XY
Anderson
L L
LL
Jacobson
C D
CD
Cheung
A K
AK
D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D001921:Brain / Q000473:pathology; D011558:Herpesvirus 1, Suid / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D009296:Nasal Cavity / Q000821:virology; D011557:Pseudorabies / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D011995:Recombination, Genetic; D017384:Sequence Deletion; D013552:Swine; D013553:Swine Diseases / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D012668:Trigeminal Ganglion / Q000473:pathology; D014774:Virulence / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
D000956:Antigens, Viral