A herpesvirus, referred to as LHV-4, was found to be associated with a disease affecting over half of the 55 rabbits on a farm near Anchorage, Alaska. About 28% of the affected animals died or were euthanized because of the severity of the illness. Extracts from the skin of infected rabbits produced syncytia and cell lysis in cultured rabbit skin and kidney cells, and in Vero cells. PCR using degenerative primers to conserved herpesvirus genes was used to amplify sequences from purified viral DNA. Sequencing of these products allowed the design of specific primers so that complete sequence data for a number of genes could be determined. Analysis of this sequence data indicates that the virus is a member of the simplex genus of herpesviruses and is most closely related to bovine herpesvirus 2, HSV-1, HSV-2, and cercopithecine herpesvirus. Experimental exposure of New Zealand White rabbits to the isolate resulted in severe eye disease and necrosis of the spleen and lymph nodes. In addition, viral DNA was identified in a variety of tissues by PCR during the acute infection (within 5 days post- infection), but was only detectable consistently in trigeminal ganglia (TG) after 14 days post- infection. Experimental exposure of Swiss Webster mice to the isolate at 1X103 PFU/eye resulted in mild eye disease and fever. Viral DNA was detected in spleen tissue during the acute infection, and was detectable in the TG after 20 day post-infection. One of the unique features of alphaherpes virus is that they become latent in the TG with no gene expression, except for the latency associated transcript gene (LAT). The role of LAT during latency is still not well understood. The LAT gene may be the key to understand the mechanism of HSV-1 or HSV-2 latency reactivation. The purpose of the research outlined in this proposal is to investigate LAT gene of this novel herpesvirus. To accomplish this we will sequence and annotate the genomes of LHV-4 and characterize the LAT region. Because of its close relationship to the primate virus lineage, and its ability to infect rabbits, information on latency in this virus may provide a natural host model system for understanding latency in herpesvirus infections of humans.
In this research application we propose to sequence the genome of a recently discovered Simplex herpesvirus pathogenic for rabbits that is closely related to HSV-1 and 2. The goal of this research is to characterize the latency associated transcript gene (LAT) region and investigate the role of LAT during latency in a natural host model system. .
| Babra, Bobby; Watson, Gregory; Xu, Wayne et al. (2012) Analysis of the genome of leporid herpesvirus 4. Virology 433:183-91 |
