Study of immunogenicity and virulence of bovine herpesvirus 1 mutants deficient in the UL49 homolog, UL49.5 homolog and dUTPase genes in cattle

Liang, Xiaoping; Chow, Betty; Babiuk, Lorne A.

doi:10.1016/s0264-410x(97)00008-x

Cited by 33 publications

(31 citation statements)

References 24 publications

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“…Although gC is the candidate protein to interact firstly with the host cells [109,110,112,113,151,152], its function in BoHV-1 pathogenesis is not elucidated. Whereas gC expression was shown as a major determinant for viral replication in the skin and plays a critical role in the virulence of human alphaherpesvirus VZV [140], gC is not essential for BoHV-1 infectivity.…”

Section: Entry and Tropismmentioning

confidence: 99%

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

et al. 2007

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-Bovine herpesvirus 1 (BoHV-1), classified as an alphaherpesvirus, is a major pathogen of cattle. Primary infection is accompanied by various clinical manifestations such as infectious bovine rhinotracheitis, abortion, infectious pustular vulvovaginitis, and systemic infection in neonates. When animals survive, a life-long latent infection is established in nervous sensory ganglia. Several reactivation stimuli can lead to viral re-excretion, which is responsible for the maintenance of BoHV-1 within a cattle herd. This paper focuses on an updated pathogenesis based on a molecular characterization of BoHV-1 and the description of the virus cycle. Special emphasis is accorded to the impact of the latency and reactivation cycle on the epidemiology and the control of BoHV-1. Several European countries have initiated BoHV-1 eradication schemes because of the significant losses incurred by disease and trading restrictions. The vaccines used against BoHV-1 are described in this context where the differentiation of infected from vaccinated animals is of critical importance to achieve BoHV-1 eradication.

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Section: Entry and Tropismmentioning

confidence: 99%

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

et al. 2007

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“…VP22 is a viral tegument protein encoded by the UL49 gene. The VP22 gene is dispensable for virus growth in vitro, but the attenuation of the VP22 deletion mutant virus in infected cattle suggests that it may play a functional role in vivo (22).…”

Section: Resultsmentioning

confidence: 99%

“…VP22 relocates to a novel subcellular site with another tegument protein, VP16, in coexpressing cells (7). In addition, a BHV-1 VP22 deletion mutant is asymptomatic and avirulent (22), suggesting that VP22 plays a functional role in virus replication in vivo.…”

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confidence: 99%

Tyrosine Phosphorylation of Bovine Herpesvirus 1 Tegument Protein VP22 Correlates with the Incorporation of VP22 into Virions

Ren

Harms

Splitter

2001

J Virol

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Tyrosine phosphorylation has been shown to play a role in the replication of several herpesviruses. In this report, we demonstrate that bovine herpesvirus 1 infection triggered tyrosine phosphorylation of proteins with molecular masses similar to those of phosphorylated viral structural proteins. One of the tyrosine-phosphorylated viral structural proteins was the tegument protein VP22. A tyrosine 38-to-phenylalanine mutation totally abolished the phosphorylation of VP22 in transfected cells. However, construction of a VP22 tyrosine 38-tophenylalanine mutant virus demonstrated that VP22 was still phosphorylated but that the phosphorylation site may change to the C terminus rather than be in the N terminus as in wild-type VP22. In addition, the loss of VP22 tyrosine phosphorylation correlated with reduced incorporation of VP22 compared to that of envelope glycoprotein D in the mutant viruses but not with the amount of VP22 produced during virus infection. Our data suggest that tyrosine phosphorylation of VP22 plays a role in virion assembly.The tegument is a unique feature of herpesviruses and remains the least well-characterized virion compartment (41).There are approximately 15 virally encoded proteins that participate in the assembly of the amorphous tegument structure, and these tegument proteins occupy the majority of the mass in the virion (18,25,40). Recent studies have shown that at least a portion of the tegument structure has an ordered organization and interacts with the capsid (37,42,43,47,48); however, little is known regarding the acquisition of the viral tegument process (14,15,36,38,41). The incorporation of herpes simplex virus type 1 (HSV-1) tegument protein VP22 is increased more than twofold when the VP22 protein expression level is increased fivefold (21). This observation is consistent with the hypothesis that the incorporation of tegument protein is partly determined by local protein concentration. In contrast, the amount of HSV-1 tegument protein UL37 in virions is strictly controlled despite a 20-fold increase of UL37 in infected cells (25). Thus, multiple mechanisms to control the incorporation of different tegument proteins may exist. In addition, evidence suggests that acquisition of the tegument is independent of capsid or envelope (26, 36). The tegument retains its structural integrity in the absence of the capsid and envelope, indicating strong intermolecular interactions that must exist between these tegument proteins to support the seemingly amorphous structure (7,27,40).Most of the herpesvirus tegument proteins are phosphoproteins (3,11,12,20,41). Phosphorylation of tegument proteins is believed to play a role in tegument protein dissociation (28). Both cellular and virally encoded kinases are involved in the phosphorylation of tegument proteins (5, 11, 12), and serines of tegument protein HSV-1 VP22 are phosphorylated in infected cells (11,12). Phosphorylation of VP22 coincides with the translocation of VP22 into the nuclei of HSV-1-infected cells (10,19,28,32,33). Interestingly...

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“…A herpes simplex virus-1 mutant expressing a truncated form of VP22 has been characterized (2). Interestingly a deletion mutant of VP22 is avirulent in infected cattle, suggesting that VP22 is an important virulence factor and may play a modulatory role in BHV-1 in vivo infection (3).…”

Section: From the Departments Of ‡ Animal Health And Biomedical Scienmentioning

confidence: 99%

Nuclear and Mitochondrial Localization Signals Overlap within Bovine Herpesvirus 1 Tegument Protein VP22

Zhu¹,

Qiu²,

Wiese

et al. 2005

Journal of Biological Chemistry

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VP22, a tegument protein of bovine herpesvirus 1, accumulates in the nucleus of infected and transiently transfected cells. Previous studies indicated a possible regulatory function of VP22 within nuclei, but how VP22 enters nuclei is unknown. Despite the abundance of basic residues within this protein, no classic nuclear localization signal (NLS) motif has been identified. To identify the signal directing nuclear accumulation, a series of truncations, internal deletions, and point mutations were constructed. Fluorescence microscopy of cells transfected with VP22 constructs indicated that a sequence of 103 residues is necessary and sufficient for nuclear localization. This NLS sequence is conformation-sensitive in contrast to a classical sequential NLS. Energy depletion assays and co-immunoprecipitation suggested that this NLS sequence also binds histone H4, resulting in nuclear retention of VP22. In addition, a mitochondrial targeting sequence was identified at the C-terminal 49 amino acids, which overlapped the sequence required for nuclear targeting. Our findings demonstrate the diversity of VP22 protein to localize within the cell and provide the opportunity for VP22 to direct cargo specifically to different subcellular compartments.VP22 is a major component of the herpesvirus tegument, a viral compartment located between the capsid and envelope. As is true for many viral tegument proteins, the function of VP22 in viral replication and infection is yet to be elucidated. Bovine herpesvirus 1 (BHV-1) 1 VP22 is dispensable for viral growth in cell culture, but deletion of VP22 from the virus genome delays virus growth and greatly reduces virus yield (1). A herpes simplex virus-1 mutant expressing a truncated form of VP22 has been characterized (2). Interestingly a deletion mutant of VP22 is avirulent in infected cattle, suggesting that VP22 is an important virulence factor and may play a modulatory role in BHV-1 in vivo infection (3).Although VP22 has no "classical" nuclear localization signal (NLS), it accumulates in the nucleus of infected cells by an unknown mechanism. In the nucleus, VP22 associates with a variety of viral and cellular factors. For example, VP22 binds VP16, an important viral transactivator of early gene expression, and is considered to regulate the function of VP16 (4). VP22 also interacts with template-activating factor I, a chromatin-remodeling protein. Template-activating factor I promotes an ordered transfer of histones to naked DNA, and binding of VP22 to template-activating factor I may regulate the function of template-activating factor I and interfere with nucleosomal deposition of the virus genome in early infection (5). We previously reported that BHV VP22 also binds nucleosomes, interfering with acetylation of histone H4 (6), suggesting a possible regulatory role of VP22 in virus infection. Interestingly expression of VP22 in transfected cells up-regulates the expression ratio of Bax/Bcl-2 inducing apoptosis (7). In addition, herpes simplex virus VP22 can bind and traffic mRNA t...

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Study of immunogenicity and virulence of bovine herpesvirus 1 mutants deficient in the UL49 homolog, UL49.5 homolog and dUTPase genes in cattle

Cited by 33 publications

References 24 publications

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

Tyrosine Phosphorylation of Bovine Herpesvirus 1 Tegument Protein VP22 Correlates with the Incorporation of VP22 into Virions

Nuclear and Mitochondrial Localization Signals Overlap within Bovine Herpesvirus 1 Tegument Protein VP22

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