Virion-Wide Protein Interactions of Kaposi's Sarcoma-Associated Herpesvirus

Rozen, Ramona; Sathish, Narayanan; Li, Yong; Yuan, Yan

doi:10.1128/jvi.02745-07

Cited by 99 publications

(122 citation statements)

References 28 publications

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“…According to structural analysis (4), pORF52 functions as a dimer and the N-terminal ␣-helix is likely involved in interactions with other components. Immunoprecipitation assays revealed that pORF52 interacts with pORF33, pORF75, gM, and gN in KSHV (47) and with pORF42 in MuHV-4 (57). The results obtained in the present study suggest that it is also a very abundant and important component of BoHV-4 virion.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Characterization of Bovine Herpesvirus 4 Extracellular Virions

Lété

Palmeira

Leroy

et al. 2012

J Virol

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cGammaherpesviruses are important pathogens in human and animal populations. During early events of infection, these viruses manipulate preexisting host cell signaling pathways to allow successful infection. The different proteins that compose viral particles are therefore likely to have critical functions not only in viral structures and in entry into target cell but also in evasion of the host's antiviral response. In this study, we analyzed the protein composition of bovine herpesvirus 4 (BoHV-4), a close relative of the human Kaposi's sarcoma-associated herpesvirus. Using mass spectrometry-based approaches, we identified 37 viral proteins associated with extracellular virions, among which 24 were resistant to proteinase K treatment of intact virions. Analysis of proteins associated with purified capsid-tegument preparations allowed us to define protein localization. In parallel, in order to identify some previously undefined open reading frames, we mapped peptides detected in whole virion lysates onto the six frames of the BoHV-4 genome to generate a proteogenomic map of BoHV-4 virions. Furthermore, we detected important glycosylation of three envelope proteins: gB, gH, and gp180. Finally, we identified 38 host proteins associated with BoHV-4 virions; 15 of these proteins were resistant to proteinase K treatment of intact virions. Many of these have important functions in different cellular pathways involved in virus infection. This study extends our knowledge of gammaherpesvirus virions composition and provides new insights for understanding the life cycle of these viruses.

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Section: Discussionmentioning

confidence: 99%

Proteomic Characterization of Bovine Herpesvirus 4 Extracellular Virions

Lété

Palmeira

Leroy

et al. 2012

J Virol

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“…Because ORF45 is a virion tegument protein, it is expected to interact with other virion proteins in various stages of the viral life cycle. Indeed, a recent virion-wide interaction screening has revealed that ORF45 interacts with capsid protein ORF62, tegument proteins ORF63, and ORF64 (55). ORF45 has also been found to interact with RTA in another viral genome-wide interaction screening (56).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Sustained Activation of Ribosomal S6 Kinase (RSK) and ERK by Kaposi Sarcoma-associated Herpesvirus ORF45

Kuang

Zhu

2009

Journal of Biological Chemistry

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As obligate intracellular parasites, viruses exploit diverse cellular signaling machineries, including the mitogen-activated protein-kinase pathway, during their infections. We have demonstrated previously that the open reading frame 45 (ORF45) of Kaposi sarcoma-associated herpesvirus interacts with p90 ribosomal S6 kinases (RSKs) and strongly stimulates their kinase activities (Kuang, E., Tang, Q., Maul, G. G., and Zhu, F. (2008) J. Virol. 82, 1838 -1850). Here, we define the mechanism by which ORF45 activates RSKs. We demonstrated that binding of ORF45 to RSK increases the association of extracellular signalregulated kinase (ERK) with RSK, such that ORF45, RSK, and ERK formed high molecular mass protein complexes. We further demonstrated that the complexes shielded active pERK and pRSK from dephosphorylation. As a result, the complex-associated RSK and ERK were activated and sustained at high levels. Finally, we provide evidence that this mechanism contributes to the sustained activation of ERK and RSK in Kaposi sarcomaassociated herpesvirus lytic replication.The extracellular signal-regulated kinase (ERK) 2 mitogenactivated protein kinase (MAPK) signaling pathway has been implicated in diverse cellular physiological processes including proliferation, survival, growth, differentiation, and motility (1-4) and is also exploited by a variety of viruses such as Kaposi sarcoma-associated herpesvirus (KSHV), human cytomegalovirus, human immunodeficiency virus, respiratory syncytial virus, hepatitis B virus, coxsackie, vaccinia, coronavirus, and influenza virus (5-17). The MAPK kinases relay the extracellular signaling through sequential phosphorylation to an array of cytoplasmic and nuclear substrates to elicit specific responses (1, 2, 18). Phosphorylation of MAPK is reversible. The kinetics of deactivation or duration of signaling dictates diverse biological outcomes (19,20). For example, sustained but not transient activation of ERK signaling induces the differentiation of PC12 cells into sympathetic-like neurons and transformation of NIH3T3 cells (20 -22). During viral infection, a unique biphasic ERK activation has been observed for some viruses (an early transient activation triggered by viral binding or entry and a late sustained activation correlated with viral gene expression), but the responsible viral factors and underlying mechanism for the sustained ERK activation remain largely unknown (5,8,13,23).The p90 ribosomal S6 kinases (RSKs) are a family of serine/ threonine kinases that lie at the terminus of the ERK pathway (1, 24 -26). In mammals, four isoforms are known, RSK1 to RSK4. Each one has two catalytically functional kinase domains, the N-terminal kinase domain (NTKD) and C-terminal kinase domain (CTKD) as well as a linker region between the two. The NTKD is responsible for phosphorylation of exogenous substrates, and the CTKD and linker region regulate RSK activation (1,24,25). In quiescent cells ERK binds to the docking site in the C terminus of RSK (27-29). Upon mitogen stimulation, ERK is activ...

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“…However, future research on tegument will require identifying herpesviral protein-protein interaction and herpesviral protein-cellular protein interaction maps during the course of infecting host cells and validating such interactions by viral genetics approach. This has been done to some extent with the Alphaherpesvirinae subfamily member VZV and the Gammaherpesvirinae subfamily members KSHV and EBV (Uetz et al, 2006;Calderwood et al, 2007;Rozen et al, 2008). Such information will improve our understanding of the biology of herpesvirus and the roles of tegument proteins.…”

Section: Discussionmentioning

confidence: 99%

Role of tegument proteins in herpesvirus assembly and egress

et al. 2010

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Morphogenesis and maturation of viral particles is an essential step of viral replication. An infectious herpesviral particle has a multilayered architecture, and contains a large DNA genome, a capsid shell, a tegument and an envelope spiked with glycoproteins. Unique to herpesviruses, tegument is a structure that occupies the space between the nucleocapsid and the envelope and contains many virus encoded proteins called tegument proteins. Historically the tegument has been described as an amorphous structure, but increasing evidence supports the notion that there is an ordered addition of tegument during virion assembly, which is consistent with the important roles of tegument proteins in the assembly and egress of herpesviral particles. In this review we first give an overview of the herpesvirus assembly and egress process. We then discuss the roles of selected tegument proteins in each step of the process, i.e., primary envelopment, deenvelopment, secondary envelopment and transport of viral particles. We also suggest key issues that should be addressed in the near future.

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Virion-Wide Protein Interactions of Kaposi's Sarcoma-Associated Herpesvirus

Cited by 99 publications

References 28 publications

Proteomic Characterization of Bovine Herpesvirus 4 Extracellular Virions

Proteomic Characterization of Bovine Herpesvirus 4 Extracellular Virions

Mechanism of Sustained Activation of Ribosomal S6 Kinase (RSK) and ERK by Kaposi Sarcoma-associated Herpesvirus ORF45

Role of tegument proteins in herpesvirus assembly and egress

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