PMID- 12663791
OWN - NLM
STAT- MEDLINE
DCOM- 20030505
LR  - 20240410
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 77
IP  - 8
DP  - 2003 Apr
TI  - Infection of cattle with a bovine herpesvirus 1 strain that contains a mutation 
      in the latency-related gene leads to increased apoptosis in trigeminal ganglia 
      during the transition from acute infection to latency.
PG  - 4848-57
AB  - Bovine herpesvirus 1 (BHV-1) is an important pathogen of cattle and infection is 
      usually initiated via the ocular or nasal cavity. After acute infection, the 
      primary site for BHV-1 latency is sensory neurons in the trigeminal ganglia (TG). 
      Reactivation from latency occurs sporadically, resulting in virus shedding and 
      transmission to uninfected cattle. The only abundant viral transcript expressed 
      during latency is the latency-related (LR) RNA. An LR mutant was constructed by 
      inserting three stop codons near the beginning of the LR RNA. This mutant grows 
      to wild-type (wt) efficiency in bovine kidney cells and in the nasal cavity of 
      acutely infected calves. However, shedding of infectious virus from the eye and 
      TG was dramatically reduced in calves infected with the LR mutant. Calves 
      latently infected with the LR mutant do not reactivate after dexamethasone 
      treatment. In contrast, all calves latently infected with wt BHV-1 or the LR 
      rescued mutant reactivate from latency after dexamethasone treatment. In the 
      present study, we compared the frequency of apoptosis in calves infected with the 
      LR mutant to calves infected with wt BHV-1 because LR gene products inhibit 
      apoptosis in transiently transfected cells. A sensitive TUNEL (terminal 
      deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay and an 
      antibody that detects cleaved caspase-3 were used to identify apoptotic cells in 
      TG. Both assays demonstrated that calves infected with the LR mutant for 14 days 
      had higher levels of apoptosis in TG compared to calves infected with wt BHV-1 or 
      to mock-infected calves. Viral gene expression, except for the LR gene, is 
      extinguished by 14 days after infection, and thus this time frame is 
      operationally defined as the establishment of latency. Real-time PCR analysis 
      indicated that lower levels of viral DNA were present in the TG of calves 
      infected with the LR mutant throughout acute infection. Taken together, these 
      results suggest that the antiapoptotic properties of the LR gene play an 
      important role during the establishment of latency.
FAU - Lovato, Luciane
AU  - Lovato L
AD  - Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, 
      University of Nebraska at Lincoln, Lincoln, Nebraska 68583-0905,USA.
FAU - Inman, Melissa
AU  - Inman M
FAU - Henderson, Gail
AU  - Henderson G
FAU - Doster, Alan
AU  - Doster A
FAU - Jones, Clinton
AU  - Jones C
LA  - eng
GR  - P20 RR015635/RR/NCRR NIH HHS/United States
GR  - P20RR15635/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - *Apoptosis
MH  - Cattle
MH  - Cattle Diseases/*virology
MH  - Cell Line
MH  - Herpesviridae Infections/veterinary/virology
MH  - Herpesvirus 1, Bovine/genetics/*pathogenicity
MH  - In Situ Nick-End Labeling
MH  - *Mutation
MH  - Neurons/virology
MH  - Trigeminal Ganglion/cytology/*virology
MH  - Viral Proteins/genetics
MH  - Virus Activation
MH  - Virus Latency/*genetics
PMC - PMC152160
EDAT- 2003/03/29 05:00
MHDA- 2003/05/06 05:00
PMCR- 2003/04/01
CRDT- 2003/03/29 05:00
PHST- 2003/03/29 05:00 [pubmed]
PHST- 2003/05/06 05:00 [medline]
PHST- 2003/03/29 05:00 [entrez]
PHST- 2003/04/01 00:00 [pmc-release]
AID - 2268 [pii]
AID - 10.1128/jvi.77.8.4848-4857.2003 [doi]
PST - ppublish
SO  - J Virol. 2003 Apr;77(8):4848-57. doi: 10.1128/jvi.77.8.4848-4857.2003.