scholarly journals The Proteoglycan Form of Bovine Herpesvirus 1 and Bovine Herpesvirus 5 Glycoprotein G Gene Products: A Novel Modification for Herpesviral Glycoproteins.

1997 ◽  
Vol 9 (48) ◽  
pp. 331-338
Author(s):  
Günther M. Keil
1999 ◽  
Vol 73 (12) ◽  
pp. 9734-9740 ◽  
Author(s):  
Janice Ciacci-Zanella ◽  
Melissa Stone ◽  
Gail Henderson ◽  
Clinton Jones

ABSTRACT Although viral gene expression occurs in the peripheral nervous system during acute infection, bovine herpesvirus 1 (BHV-1) gene expression is extinguished, many neurons survive, and latency ensues. The only abundant viral transcript expressed during latency is the latency-related (LR) RNA, which is alternatively spliced in trigeminal ganglia during acute infection (L. Devireddy and C. Jones, J. Virol. 72:7294–7301, 1998). A subset of neurons express a protein encoded by the LR gene and the LR protein (LRP) is associated with cyclin-dependent kinase 2 (Cdk2)/cyclin complexes during productive infection (Y. Jiang, A. Hossain, M. T. Winkler, T. Holt, A. Doster, and C. Jones, J. Virol. 72:8133–8142, 1998). LR gene products inhibit cell cycle progression, perhaps as a result of LRP interacting with Cdk2/cyclin complexes. During acute infection, expression of cyclin A occurs in trigeminal ganglionic neurons (L. M. Schang, A. Hossain, and C. Jones, J. Virol. 70:3807–3814, 1996). Inappropriate expression of G1- and S-phase cyclins can initiate programmed cell death (PCD), apoptosis, in neurons, suggesting that LR gene products inhibit PCD. To test this hypothesis, we modified an assay to measure PCD frequency in transiently transfected cells. C6-ceramide, fumonisin B1(FB1), or etoposide was used to initiate PCD following transfection of cells with plasmids expressing LR gene products and the β-galactosidase gene. Transfected cells that survived were quantified by counting β-galactosidase-positive cells. Plasmids that expressed LR gene products promoted survival of monkey kidney (CV-1), human lung (IMR-90), or mouse neuroblastoma (neuro-2A) cells after induction of PCD. Plasmids with termination codons at the beginning of LR open reading frames or deletion of sequences that mediate splicing of LR RNA did not promote cell survival following PCD induction. We hypothesize that LR gene products play a role in promoting survival of postmitotic neurons during acute infection or reactivation.


2013 ◽  
Vol 19 (1) ◽  
pp. 276-285 ◽  
Author(s):  
Zheng Liu ◽  
Ramalingam Bethunaickan ◽  
Ranjit Sahu ◽  
Max Brenner ◽  
Teresina Laragione ◽  
...  

2021 ◽  
Vol 22 (2) ◽  
pp. 519
Author(s):  
Jing Zhao ◽  
Nishani Wijesekera ◽  
Clinton Jones

The ability to establish, maintain, and reactivate from latency in sensory neurons within trigeminal ganglia (TG) is crucial for bovine herpesvirus 1 (BoHV-1) transmission. In contrast to lytic infection, the only viral gene abundantly expressed during latency is the latency-related (LR) gene. The synthetic corticosteroid dexamethasone consistently induces reactivation from latency, in part because the glucocorticoid receptor (GR) transactivates viral promoters that drive expression of key viral transcriptional regulator proteins (bICP0 and bICP4). Within hours after dexamethasone treatment of latently infected calves, LR gene products and β-catenin are not readily detected in TG neurons. Hence, we hypothesized that LR gene products and/or β-catenin restrict GR-mediated transcriptional activation. A plasmid expressing LR RNA sequences that span open reading frame 2 (ORF2-Stop) inhibited GR-mediated transactivation of the BoHV-1 immediate early transcription unit 1 (IEtu1) and mouse mammary tumor virus (MMTV) promoter activity in mouse neuroblastoma cells (Neuro-2A). ORF2-Stop also reduced productive infection and GR steady-state protein levels in transfected Neuro-2A cells. Additional studies revealed that the constitutively active β-catenin mutant reduced the transactivation of the IEtu1 promoter by GR and dexamethasone. Collectively, these studies suggest ORF2 RNA sequences and Wnt/β-catenin signaling pathway actively promote maintenance of latency, in part, by impairing GR-mediated gene expression.


2001 ◽  
Vol 75 (18) ◽  
pp. 8507-8515 ◽  
Author(s):  
Melissa Inman ◽  
Luciane Lovato ◽  
Alan Doster ◽  
Clinton Jones

ABSTRACT Bovine herpesvirus 1 (BHV-1) is an important pathogen of cattle, and infection is usually initiated in the ocular or nasal cavity. Like other alphaherpesviruses, BHV-1 establishes latency in sensory neurons but has the potential of reactivating from latency and spreading. The only abundant viral transcript expressed during latency is the latency-related (LR) RNA, which is alternatively spliced in trigeminal ganglia during acute infection (L. R. Devireddy and C. Jones, J. Virol. 72:7294–7301, 1998). LR gene products inhibit cell cycle progression (Y. Jiang, A. Hossain, M. T. Winkler, T. Holt, A. Doster, and C. Jones, J. Virol. 72:8133–8142, 1998) and chemically induced apoptosis (J. Ciacci-Zannela, M. Stone, G. Henderson, and C. Jones. J. Virol. 73:9734–9740, 1999). Although these studies suggest that LR gene products play an important role in the latency/pathogenesis of BHV-1, construction of a mutant is necessary to test this hypothesis. Because the bICP0 gene overlaps and is antisense to the LR gene, it was necessary to mutate the LR gene without altering bICP0 expression. This was accomplished by inserting three stop codons near the beginning of the LR RNA, thus interfering with expression of proteins expressed by the LR RNA. The LR mutant virus grew with wild-type (WT) efficiency in bovine kidney (MDBK) cells and expressed bICP0 at least as efficiently as WT BHV-1 or the LR rescued virus. When calves were infected with the LR mutant, we observed a dramatic decrease (3 to 4 log units) in ocular shedding during acute infection relative to WT or the LR rescued virus. In contrast, shedding of the LR mutant from the nasal cavity was not significantly different from that of the WT or the LR rescued virus. Calves infected with the LR mutant exhibited mild clinical symptoms, but they seroconverted. Neutralizing antibody titers were lower in calves infected with the LR mutant, confirming reduced growth. In summary, this study suggests that an LR protein promotes ocular shedding during acute infection of calves.


1998 ◽  
Vol 72 (5) ◽  
pp. 3804-3811 ◽  
Author(s):  
Gisela Kühnle ◽  
Astrid Heinze ◽  
Jutta Schmitt ◽  
Katrin Giesow ◽  
Geraldine Taylor ◽  
...  

ABSTRACT The bovine herpesvirus 1 (BHV-1) recombinants BHV-1/eGori and BHV-1/eGsyn were isolated after insertion of expression cassettes which contained either a genomic RNA-derived cDNA fragment (BHV-1/eGori) or a modified, chemically synthesized open reading frame (ORF) (BHV-1/eGsyn), which both encode the attachment glycoprotein G of bovine respiratory syncytial virus (BRSV), a class II membrane glycoprotein. Northern blot analyses and nuclear runoff transcription experiments indicated that transcripts encompassing the authentic BRSV G ORF were unstable in the nucleus of BHV-1/eGori-infected cells. In contrast, high levels of BRSV G RNA were detected in BHV-1/eGsyn-infected cells. Immunoblots showed that the BHV-1/eGsyn-expressed BRSV G glycoprotein contains N- and O-linked carbohydrates and that it is incorporated into the membrane of infected cells and into the envelope of BHV-1/eGsyn virions. The latter was also demonstrated by neutralization of BHV-1/eGsyn infectivity by monoclonal antibodies or polyclonal anti-BRSV G antisera and complement. Our results show that expression of the BRSV G glycoprotein by BHV-1 was dependent on the modification of the BRSV G ORF and indicate that incorporation of class II membrane glycoproteins into BHV-1 virions does not necessarily require BHV-1-specific signals. This raises the possibility of targeting heterologous polypeptides to the viral envelope, which might enable the construction of BHV-1 recombinants with new biological properties and the development of improved BHV-1-based live and inactivated vector vaccines.


Virology ◽  
2001 ◽  
Vol 279 (2) ◽  
pp. 488-498 ◽  
Author(s):  
Kazuo Nakamichi ◽  
Daisuke Kuroki ◽  
Yasunobu Matsumoto ◽  
Haruki Otsuka

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