title: Latency-related gene encoded by bovine herpesvirus 1 promotes virus growth and reactivation from latency in tonsils of infected calves.
abstract: Infection of calves with bovine herpesvirus 1 (BHV-1) results in transient immunosuppression that may lead to bacterium-induced pneumonia and, occasionally, death. Although sensory neurons in the trigeminal ganglia (TG) are the primary site of BHV-1 latency, viral genomes are detected in the tonsils of latently infected calves. Dexamethasone (DEX) consistently induces reactivation from latency, and viral gene expression is detected in TG and tonsils. In sensory neurons of latently infected calves, the latency-related (LR) gene is abundantly expressed and is required for reactivation from latency. In the present study, we compared the abilities of wild-type (wt) BHV-1 and a strain with a mutation in the LR gene (the LR mutant strain) to grow in the tonsils of infected calves and reactivate from latency. Lower levels of the LR mutant virus were detected in the tonsils of acutely infected calves. LR mutant viral DNA was consistently detected by PCR in the tonsils of latently infected calves, suggesting that the establishment of a latent or persistent infection occurred. Although the LR mutant did not reactivate from latency in vivo after DEX treatment, explantation of tonsil tissue from calves latently infected with the LR mutant yielded infectious virus. Relative to wt BHV-1, the LR mutant did not induce explant-induced reactivation as efficiently. These studies indicate that the LR gene promotes virus shedding from tonsil tissue during acute infection and reactivation from latency in tonsil tissue in vivo. We suggest that incorporation of the LR gene mutation into existing modified live vaccines would prevent reactivation from latency in neural and nonneural sites and would thus prevent transmission to other animals.
authors.affiliation: Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, Fair Street at East Campus Loop, Lincoln, NE 68583-0905, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Perez
authors.forename: Melissa
authors.initials: M
authors.lastname: Inman
authors.forename: Alan
authors.initials: A
authors.lastname: Doster
authors.forename: Clinton
authors.initials: C
authors.lastname: Jones
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D002417:Cattle; D002418:Cattle Diseases / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D007242:Herpesvirus 1, Bovine / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D009154:Mutation; D014066:Palatine Tonsil / Q000473:pathology / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014775:Virus Activation; D017735:Virus Latency
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins; C401822:latency-related protein, Bovine herpesvirus 1