A protein encoded by the bovine herpesvirus 1 open reading frame E gene induces neurite-like morphological changes in mouse neuroblastoma cells and is expressed in trigeminal ganglionic neurons.
Bovine herpes virus 1 (BHV-1), like other alpha-herpesvirinae subfamily members, establishes latency in sensory neurons. Periodically BHV-1 reactivates from latency, resulting in virus shedding and spread to uninfected cattle. Although reactivation from latency does not usually lead to recurrent disease, the latency-reactivation cycle is crucial for virus transmission. The latency-related (LR) RNA is abundantly expressed during latency, and expression of a LR encoded protein is necessary for dexamethasone-induced reactivation from latency in cattle. Within LR promoter sequences, a small open reading frame (ORF) was identified (ORF-E) that is antisense to the LR-RNA, and downstream of the bICP0 gene. ORF-E transcription is consistently detected in trigeminal ganglia (TG) of latently infected calves, suggesting ORF-E expression plays a role in the latency-reactivation cycle. Polyclonal antiserum directed against an ORF-E peptide or the entire ORF-E protein specifically recognizes the nucleus of sensory neurons in TG of latently infected calves. The ORF-E peptide-specific antiserum also recognizes a protein when mouse neuroblastoma cells (neuro-2A) are transfected with an ORF-E expression construct. In contrast to the growth inhibiting properties of the LR gene, stably transfected ORF-E-expressing cells were obtained. Neuro-2A cells stably transfected with a plasmid expressing ORF-E induced morphological changes that resembled neurite-like projections. In contrast, neurite-like projections were not observed following transfection of neuro-2A cells with an empty vector. These studies suggest that a protein encoded by ORF-E has the potential to alter the physiology or metabolism of neuronal cell types, which may be important for long-term latency.
Perez
Sandra
S
Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska 68583-0905, USA.
Meyer
Florencia
F
Henderson
Gail
G
Jiang
Yunquan
Y
Sherman
Simon
S
Doster
Alan
A
Inman
Melissa
M
Jones
Clinton
C
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000473:pathology / Q000821:virology*; D002460:Cell Line; D006566:Herpesviridae Infections / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D007242:Herpesvirus 1, Bovine / Q000737:chemistry / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D008969:Molecular Sequence Data; D016501:Neurites / Q000473:pathology*; D016366:Open Reading Frames / Q000502:physiology; D014162:Transfection; D012668:Trigeminal Ganglion / Q000378:metabolism*; D014760:Viral Fusion Proteins / Q000502:physiology*; D014764:Viral Proteins / Q000502:physiology*; D017735:Virus Latency
D014760:Viral Fusion Proteins; D014764:Viral Proteins