Pseudorabies Virus Latency Associated Transcript Gene: Expression, Regulation, and Role in the Establishment of Latency in Swine
One unique biological feature about herpesvirus infections is that they can become latent following the primary infection. Studies presented in Chapter 1 demonstrate that the PrV latency associated transcripts (LAT) gene is also active during an in vitro productive infection. Three polyadenylated [poly(A)] RNAs (about 1.0, 2.0, and 8.0 kb) made during a lytic in vitroinfection share similar physical properties with the in vivo LATs. The 1.0 and 8.0 kb RNAs partially overlap the first and second exon coding sequences of the in vivo 8.4 kb LAT (LLT), respectively. The entire 2.0 kb RNA overlaps the LLT and has the same intron removed as that in LLT. This 2.0 kb RNA starts about 243 bp downstream of the start site of the LLT, and terminates around the junction of Bam HI 8' and 8. Whether or not LAT expression is required for the establishment of latency was investigated using mutants lacking the PrV LAT promoter (Chapter 2). The study indicates that the lack of LAT expression does not affect the establishment of viral latency in the natural host animal, swine. In addition, PrV LAT gene, expression was found not to be solely regulated by one promoter. A further area of inquiry was concerned with whether there was any other viral gene responsible for establishing PrV latency. To investigate such possibility, the biological properties of a deletion mutant (PrV-dLAT/EP0) lacking both the LAT and EP0 genes were examined (Chapter 3). In vitro and in vivo studies indicated that this dual deletion mutant replicated less efficiently than the wild type virus. Pigs infected with this mutant at a wild type lethal dose experienced a very mild disease and recovered. This mutant was capable of eliciting both antibody and cell mediated immune responses. Furthermore, the PrV-dLAT/EP0 was unable to establish latency. The studies presented in this chapter provide evidence for the first time that the PrV EP0 gene may play an essential role in latency establishment.
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