Functional Analysis of the Pseudorabies Virus UL51 Protein

Klupp, Barbara G.; Granzow, Harald; Klopfleisch, Robert; Fuchs, Walter; Kopp, Martina; Lenk, Matthias; Mettenleiter, Thomas C.

doi:10.1128/jvi.79.6.3831-3840.2005

Cited by 51 publications

(68 citation statements)

References 41 publications

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“…The phenotypes in virion morphogenesis, including aberrant accumulation of unenveloped and partially enveloped virions and the lack of enveloped virions in the cytoplasm and extracellular space, have been suggested to reflect a block in a process(es) for viral secondary envelopment (27,28,51). The results in this study indicated that UL51 and UL14 acted in the same HSV-1 secondary envelopment pathway during HSV-1 replication.…”

Section: Discussionsupporting

confidence: 59%

“…As described above, HSV-1 UL51 and UL14 are conserved throughout the Herpesviridae family (1), raising the interesting possibility that complexes of UL51 and UL14 homologues in other herpesviruses regulate viral secondary envelopment. In support of this possibility, it has been reported that UL51 homologs in alphaherpesvirus PRV and betaherpesvirus HCMV are involved in viral secondary envelopment (27,28). However, the HSV-1 UL51 domain and amino acid residues required for interaction with UL14 are conserved in alpha- herpesviruses but not in beta-and gammaherpesviruses (Fig.…”

Section: Discussionmentioning

confidence: 86%

“…Palmitoylation of UL51 has been suggested to have a role in UL51 association with cytoplasmic membranes, with UL51 topology indicating that it should be displayed on the exterior surface of cytoplasmic membranes and, therefore, on the interior surface of virions (26). UL51 homologs of porcine alphaherpesvirus pseudorabies virus (PRV) and human betaherpesvirus cytomegalovirus (HCMV) have been reported to participate in viral secondary envelopment (27,28). Although HSV-1 UL51 was shown to interact with UL7 (29) and UL7 homologs in PRV and HCMV were shown to facilitate viral secondary envelopment (30,31), it remained to be determined whether HSV-1 UL51 and UL7 are involved in viral secondary envelopment.…”

mentioning

confidence: 99%

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The Interaction between Herpes Simplex Virus 1 Tegument Proteins UL51 and UL14 and Its Role in Virion Morphogenesis

Oda

Arii

Koyanagi

et al. 2016

J Virol

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To investigate the molecular mechanism(s) by which herpes simplex virus 1 (HSV-1) tegument protein UL51 promotes viral replication, we screened for viral proteins that interact with UL51 in infected cells. Affinity purification of tagged UL51 in HSV-1-infected Vero cells was coupled with immunoblotting of the purified UL51 complexes with various antibodies to HSV-1 virion proteins. Subsequent analyses revealed that UL51 interacted with another tegument protein, UL14, in infected cells. Mutational analyses of UL51 showed that UL51 amino acid residues Leu-111, Ile-119, and Tyr-123 were required for interaction with UL14 in HSV-1-infected cells. Alanine substitutions of these UL51 amino acid residues reduced viral replication and produced an accumulation of unenveloped and partially enveloped nucleocapsids in the cytoplasm at levels comparable to those of UL51-null, UL14-null, and UL51/UL14 double-null mutations. In addition, although UL51 and UL14 colocalized at juxtanuclear domains in HSV-1-infected cells, the amino acid substitutions in UL51 produced aberrant localization of UL51 and UL14. The effects of these substitutions on localization of UL51 and UL14 were similar to those of the UL51-null and UL14-null mutations on localization of UL14 and UL51, respectively. These results suggested that the interaction between UL51 and UL14 was required for proper localization of these viral proteins in infected cells and that the UL51-UL14 complex regulated final viral envelopment for efficient viral replication. IMPORTANCEHerpesviruses contain a unique virion structure designated the tegument, which is a protein layer between the nucleocapsid and the envelope. HSV-1 has dozens of viral proteins in the tegument, which are thought to facilitate viral envelopment by interacting with other virion components. However, although numerous interactions among virion proteins have been reported, data on how these interactions facilitate viral envelopment is limited. In this study, we have presented data showing that the interaction of HSV-1 tegument proteins UL51 and UL14 promoted viral final envelopment for efficient viral replication. In particular, prevention of this interaction induced aberrant accumulation of partially enveloped capsids in the cytoplasm, suggesting that the UL51-UL14 complex acted in the envelopment process but not in an upstream event, such as transport of capsids to the site for envelopment. This is the first report showing that an interaction between HSV-1 tegument proteins directly regulated final virion envelopment. Herpesviruses have a unique virion structure designated the tegument, which is a proteinaceous layer consisting of a number of different viral proteins and is located between the nucleocapsid and the envelope (1). Herpes simplex virus 1 (HSV-1), classified in the Alphaherpesvirinae subfamily of the Herpesviridae family, is one of the best-studied members in the family and has at least 23 different viral proteins in the tegument (2).In HSV-1-infected cells, packaging of nascent progeny...

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 86%

mentioning

confidence: 99%

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The Interaction between Herpes Simplex Virus 1 Tegument Proteins UL51 and UL14 and Its Role in Virion Morphogenesis

Oda

Arii

Koyanagi

et al. 2016

J Virol

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“…On the other hand, individual deletions of tegument proteins UL11, UL37, UL47, UL48, and UL51 have all resulted in accumulation of unenveloped cytoplasmic capsids, a finding that suggests a defect in secondary envelopment (133,214,218,226,227). The UL20 membrane protein is a component of virions and plays a role in sorting mature enveloped virions from the site of secondary envelopment to be released from the cell (137).…”

Section: Egressmentioning

confidence: 99%

Molecular Biology of Pseudorabies Virus: Impact on Neurovirology and Veterinary Medicine

Pomeranz

Reynolds

Hengartner

2005

Microbiol Mol Biol Rev

724

657

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Pseudorabies virus (PRV) is a herpesvirus of swine, a member of the Alphaherpesvirinae subfamily, and the etiological agent of Aujeszky's disease. This review describes the contributions of PRV research to herpesvirus biology, neurobiology, and viral pathogenesis by focusing on (i) the molecular biology of PRV, (ii) model systems to study PRV pathogenesis and neurovirulence, (iii) PRV transsynaptic tracing of neuronal circuits, and (iv) veterinary aspects of pseudorabies disease. The structure of the enveloped infectious particle, the content of the viral DNA genome, and a step-by-step overview of the viral replication cycle are presented. PRV infection is initiated by binding to cellular receptors to allow penetration into the cell. After reaching the nucleus, the viral genome directs a regulated gene expression cascade that culminates with viral DNA replication and production of new virion constituents. Finally, progeny virions self-assemble and exit the host cells. Animal models and neuronal culture systems developed for the study of PRV pathogenesis and neurovirulence are discussed. PRV serves as a self-perpetuating transsynaptic tracer of neuronal circuitry, and we detail the original studies of PRV circuitry mapping, the biology underlying this application, and the development of the next generation of tracer viruses. The basic veterinary aspects of pseudorabies management and disease in swine are discussed. PRV infection progresses from acute infection of the respiratory epithelium to latent infection in the peripheral nervous system. Sporadic reactivation from latency can transmit PRV to new hosts. The successful management of PRV disease has relied on vaccination, prevention, and testing

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“…In keeping with its proposed role in virion formation, a number of interactions between tegument proteins among themselves and with other structural proteins have been described in PrV and other herpesviruses (reviewed in references 33 and 34). Electron microscopic studies of cells infected with mutants deleted in tegument proteins US3 (23), UL11 (27), UL16 (20), UL36 (10), UL37 (21), UL47 (28), UL48 (8), and UL51 (22) have documented the relevance of these tegument proteins for morphogenesis of PrV.…”

mentioning

confidence: 99%

Composition of Pseudorabies Virus Particles Lacking Tegument Protein US3, UL47, or UL49 or Envelope Glycoprotein E

Michael

Klupp

Mettenleiter

et al. 2006

J Virol

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Proteins located in the tegument layer of herpesvirus particles play important roles in the replicative cycle at both early and late times after infection. As major constituents of the virion, they execute important functions in particular during formation of progeny virions. These functions have mostly been elucidated by construction and analysis of mutant viruses deleted in single or multiple tegument protein-encoding genes (reviewed in the work of T. C. Mettenleiter, Virus Res. 106:167-180, 2004). However, since tegument proteins have been shown to be involved in numerous protein-protein interactions, the impact of single protein deletions on the composition of the virus particle is unknown, but they could impair correct interpretation of the results. To analyze how the absence of single virion constituents influences virion composition, we established a procedure to assay relative amounts of virion structural proteins in deletion mutants of the alphaherpesvirus Pseudorabies virus (PrV) in comparison to wild-type particles. The assay is based on the mass spectrometric quantitation of virion protein-derived peptides carrying stable isotope mass tags. After deletion of the US3, UL47, UL49, or glycoprotein E gene, relative amounts of a capsid protein (UL38), a capsid-associated protein (UL25), several tegument proteins (UL36 and UL47, if present), and glycoprotein H were unaffected, whereas the content of other tegument proteins (UL46, UL48, and UL49, if present) varied significantly. In the case of the UL48 gene product, a specific increase in incorporation of a smaller isoform was observed after deletion of the UL47 or UL49 gene, whereas a larger isoform remained unaffected. The cellular protein actin was enriched in virions of mutants deficient in any of the tegument proteins UL47, UL49, or US3. By twodimensional gel electrophoresis multiple isoforms of host cell-derived heat shock protein 70 and annexins A1 and A2 were also identified as structural components of PrV virions.

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Functional Analysis of the Pseudorabies Virus UL51 Protein

Cited by 51 publications

References 41 publications

The Interaction between Herpes Simplex Virus 1 Tegument Proteins UL51 and UL14 and Its Role in Virion Morphogenesis

The Interaction between Herpes Simplex Virus 1 Tegument Proteins UL51 and UL14 and Its Role in Virion Morphogenesis

Molecular Biology of Pseudorabies Virus: Impact on Neurovirology and Veterinary Medicine

Composition of Pseudorabies Virus Particles Lacking Tegument Protein US3, UL47, or UL49 or Envelope Glycoprotein E

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