scholarly journals The zinc ring finger in the bICP0 protein encoded by bovine herpesvirus-1 mediates toxicity and activates productive infection

2001 ◽  
Vol 82 (3) ◽  
pp. 483-492 ◽  
Author(s):  
Melissa Inman ◽  
Yange Zhang ◽  
Vicki Geiser ◽  
Clinton Jones

The bICP0 protein encoded by bovine herpesvirus 1 (BHV-1) is believed to activate transcription and consequently productive infection. Expression of full-length bICP0 protein is toxic in transiently transfected mouse neuroblastoma cells (neuro-2A) in the absence of other viral genes. However, bICP0 does not appear to directly induce apoptosis. Although bICP0 is believed to be functionally similar to the herpes simplex virus type 1-encoded ICP0, the only protein domain that is well conserved is a C3HC4 zinc ring finger located near the N terminus of both proteins. Site-specific mutagenesis of the zinc ring finger of bICP0 demonstrated that it was important for inducing aggregated chromatin structures in transfected cells and toxicity. The zinc ring finger was also required for stimulating productive infection in bovine cells and for trans-activating the thymidine kinase (TK) promoter of herpes simplex virus type 1. Deletion of amino acids spanning 356–677 of bICP0 altered subcellular localization of bICP0 and prevented trans-activation of the TK promoter. However, this deletion did not prevent trans-activation of the viral genome. Taken together, these studies indicated that bICP0 has several functional domains, including the zinc ring finger, which stimulate productive infection and influence cell survival.

2000 ◽  
Vol 74 (7) ◽  
pp. 3301-3312 ◽  
Author(s):  
Jerome S. Harms ◽  
Xiaodi Ren ◽  
Sergio C. Oliveira ◽  
Gary A. Splitter

ABSTRACT The alphaherpesvirus tegument protein VP22 has been characterized with multiple traits including microtubule reorganization, nuclear localization, and nonclassical intercellular trafficking. However, all these data were derived from studies using herpes simplex virus type 1 (HSV-1) and may not apply to VP22 homologs of other alphaherpesviruses. We compared subcellular attributes of HSV-1 VP22 (HVP22) with bovine herpesvirus 1 (BHV-1) VP22 (BVP22) using green fluorescent protein (GFP)-fused VP22 expression vectors. Fluorescence microscopy of cell lines transfected with these constructs revealed differences as well as similarities between the two VP22 homologs. Compared to that of HVP22, the BVP22 microtubule interaction was much less pronounced. The VP22 nuclear interaction varied, with a marbled or halo appearance for BVP22 and a speckled or nucleolus-bound appearance for HVP22. Both VP22 homologs associated with chromatin at various stages of mitosis and could traffic from expressing cells to the nuclei of nonexpressing cells. However, distinct qualitative differences in microtubule, nuclear, and chromatin association as well as trafficking were observed. The differences in VP22 homolog characteristics revealed in this study will help define VP22 function within HSV-1 and BHV-1 infection.


2003 ◽  
Vol 16 (1) ◽  
pp. 79-95 ◽  
Author(s):  
Clinton Jones

SUMMARY Primary infection by herpes simplex virus type 1 (HSV-1) can cause clinical symptoms in the peripheral and central nervous system, upper respiratory tract, and gastrointestinal tract. Recurrent ocular shedding leads to corneal scarring that can progress to vision loss. Consequently, HSV-1 is the leading cause of corneal blindness due to an infectious agent. Bovine herpesvirus 1 (BHV-1) has similar biological properties to HSV-1 and is a significant health concern to the cattle industry. Latency of BHV-1 and HSV-1 is established in sensory neurons of trigeminal ganglia, but latency can be interrupted periodically, leading to reactivation from latency and spread of infectious virus. The ability of HSV-1 and BHV-1 to reactivate from latency leads to virus transmission and can lead to recurrent disease in individuals latently infected with HSV-1. During latency, the only abundant HSV-1 RNA expressed is the latency-associated transcript (LAT). In latently infected cattle, the latency-related (LR) RNA is the only abundant transcript that is expressed. LAT and LR RNA are antisense to ICP0 or bICP0, viral genes that are crucial for productive infection, suggesting that LAT and LR RNA interfere with productive infection by inhibiting ICP0 or bICP0 expression. Numerous studies have concluded that LAT expression is important for the latency-reactivation cycle in animal models. The LR gene has recently been demonstrated to be required for the latency-reactivation cycle in cattle. Several recent studies have demonstrated that LAT and the LR gene inhibit apoptosis (programmed cell death) in trigeminal ganglia of infected animals and transiently transfected cells. The antiapoptotic properties of LAT map to the same sequences that are necessary for promoting reactivation from latency. This review summarizes our current knowledge of factors regulating the latency-reactivation cycle of HSV-1 and BHV-1.


2004 ◽  
Vol 78 (8) ◽  
pp. 3872-3879 ◽  
Author(s):  
François Meurens ◽  
Frédéric Schynts ◽  
Günther M. Keil ◽  
Benoît Muylkens ◽  
Alain Vanderplasschen ◽  
...  

ABSTRACT Homologous recombination between strains of the same alphaherpesvirus species occurs frequently both in vitro and in vivo. This process has been described between strains of herpes simplex virus type 1, herpes simplex virus type 2, pseudorabies virus, feline herpesvirus 1, varicella-zoster virus, and bovine herpesvirus 1 (BoHV-1). In vivo, the rise of recombinant viruses can be modulated by different factors, such as the dose of the inoculated viruses, the distance between inoculation sites, the time interval between inoculation of the first and the second virus, and the genes in which the mutations are located. The effect of the time interval between infections with two distinguishable BoHV-1 on recombination was studied in three ways: (i) recombination at the level of progeny viruses, (ii) interference induced by the first virus infection on β-galactosidase gene expression of a superinfecting virus, and (iii) recombination at the level of concatemeric DNA. A time interval of 2 to 8 h between two successive infections allows the establishment of a barrier, which reduces or prevents any successful superinfection needed to generate recombinant viruses. The dramatic effect of the time interval on the rise of recombinant viruses is particularly important for the risk assessment of recombination between glycoprotein E-negative marker vaccine and field strains that could threaten BoHV-1 control and eradication programs.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1148
Author(s):  
Fouad S. El-mayet ◽  
Kelly S. Harrison ◽  
Clinton Jones

Expression of Krüppel-like factor 15 (KLF15), a stress-induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed that KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1-immediate-early transcription unit 1 (IEtu1), herpes simplex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoters. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 expression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection, and KLF15 steady-state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following infection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene, and to a lesser extent, bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 promoter activity. Collectively, these studies revealed that HSV-1 and BoHV-1 productive infection increased KLF15 steady-state protein levels, which correlated with increased virus production.


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