Identification of the Epstein Barr Virus portal

Visalli, Robert J.; Schwartz, Adam M.; Patel, Shivam; Visalli, M

doi:10.1016/j.virol.2019.01.003

Cited by 9 publications

(5 citation statements)

References 55 publications

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“…Cryo-electron microscopy has recently provided high-resolution atomic structures of the portal vertex and the CVSC of KSHV [8,21], as well as of HSV-1 [9,10,17,22], HSV-2 [23][24][25], EBV [26,27], and VZV [28]. These models have shown that the KSHV portal vertex is enriched with the CVSC tegument complexes, and unlike the high occupancy of CVSC in all vertices of HSV-1 and HSV-2 capsids, CVSC complexes on the other 11 vertices of the KSHV capsids were only partially and flexibly occupied, reaching an average of approximately 30% occupancy.…”

Section: Introductionmentioning

confidence: 99%

The Portal Vertex of KSHV Promotes Docking of Capsids at the Nuclear Pores

Dünn-Kittenplon

Ashkenazy-Titelman

Kalt

et al. 2021

Viruses

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Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-related herpesvirus. Like other herpesviruses, the KSHV icosahedral capsid includes a portal vertex, composed of 12 protein subunits encoded by open reading frame (ORF) 43, which enables packaging and release of the viral genome into the nucleus through the nuclear pore complex (NPC). Capsid vertex-specific component (CVSC) tegument proteins, which directly mediate docking at the NPCs, are organized on the capsid vertices and are enriched on the portal vertex. Whether and how the portal vertex is selected for docking at the NPC is unknown. Here, we investigated the docking of incoming ORF43-null KSHV capsids at the NPCs, and describe a significantly lower fraction of capsids attached to the nuclear envelope compared to wild-type (WT) capsids. Like WT capsids, nuclear envelope-associated ORF43-null capsids co-localized with different nucleoporins (Nups) and did not detach upon salt treatment. Inhibition of nuclear export did not alter WT capsid docking. As ORF43-null capsids exhibit lower extent of association with the NPCs, we conclude that although not essential, the portal has a role in mediating the interaction of the CVSC proteins with Nups, and suggest a model whereby WT capsids can dock at the nuclear envelope through a non-portal penton vertex, resulting in an infection ‘dead end’.

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Section: Introductionmentioning

confidence: 99%

The Portal Vertex of KSHV Promotes Docking of Capsids at the Nuclear Pores

Dünn-Kittenplon

Ashkenazy-Titelman

Kalt

et al. 2021

Viruses

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“…The portal protein BBRF1 is a homolog of herpes simplex virus 1 (HSV-1) UL6, which is required for the encapsulation and cleavage of the viral genome. Specifically, the deletion of BBRF1 from the EBV genome has been shown to result in "empty" capsids containing no viral genome (28), and transmission electron microscopy of BBRF1 revealed the formation of a self-assembling structure consistent with other herpesvirus portals (29). Two further capsid proteins, BVRF2, a protease, and BcLF1, the major capsid protein, are both required for EBV capsid assembly (30).…”

Section: Discussionmentioning

confidence: 99%

Identifying the Cellular Interactome of Epstein-Barr Virus Lytic Regulator Zta Reveals Cellular Targets Contributing to Viral Replication

Zhou

Heesom

Osborn

et al. 2020

J Virol

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The human gammaherpesvirus Epstein-Barr virus (EBV) (human herpesvirus 4 [HHV4]) infects most adults and is an important contributor to the development of many types of lymphoid and epithelial cancers. Essential contributions of viral genes to viral replication are known, but the potential contributions of cell genes are less well delineated. A key player is the viral protein Zta (BZLF1, ZEBRA, or Z). This sequence-specific DNA-binding protein can disrupt EBV latency by driving the transcription of target genes and by interacting with the EBV lytic origin of replication. Here, we used an unbiased proteomics approach to identify the Zta-interactome in cells derived from Burkitt’s lymphoma. Isolating Zta and associated proteins from Burkitt’s lymphoma cells undergoing EBV replication, followed by tandem mass tag (TMT) mass spectrometry, resulted in the identification of 39 viral and cellular proteins within the Zta interactome. An association of Zta with the cellular protein NFATc2 was validated in independent experiments. Furthermore, the ability of Zta to attenuate the activity of an NFAT-dependent promoter was shown, which suggests a functional consequence for the association. The expression of Zta is itself regulated through NFAT activity, suggesting that Zta may contribute to a feedback loop that would limit its own expression, thus aiding viral replication by preventing the known toxic effects of Zta overexpression. IMPORTANCE Epstein-Barr virus infects most people across the world and causes several kinds of cancer. Zta is an important viral protein that makes the virus replicate by binding to its DNA and turning on the expression of some genes. We used a sensitive, unbiased approach to isolate and identify viral and cellular proteins that physically interact with Zta. This revealed 39 viral and cellular proteins. We found that one protein, termed NFATc2, was already known to be important for a very early step in viral replication. We identify that once this step has occurred, Zta reduces the effectiveness of NFATc2, and we suggest that this is important to prevent cells from dying before viral replication is complete and the mature virus is released from the cells.

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“…The mechanism for the packaging of viral double-stranded genome into the protein shell with the aid of an elegant motor is an intriguing subject. − ,,− Significant progress on the study of the mechanisms of viral DNA packaging motors has been achieved in the poxvirus, − adenovirus, − herpesvirus, − and minivirus. ,− Studies have revealed that the revolving mechanism is a common feature shared by all the dsDNA packaging motors, including SPP1, P22, T7, the HK97 family phage, and poxvirus evidenced by the results from both structural and biochemical studies. Analysis of crystal structures of the motor channels (the connectors) of SPP1, T7, HK97, P22, and Phi29 revealed that all of the motor channels displayed an antichiral arrangement between the channel and the DNA helices.…”

Section: The Left- and Right-handed Chirality Between The Revolving A...mentioning

confidence: 99%

“…The well-studied rotating motors include F1/F0 ATPase, − DNA helicase, , Rho transcription termination factor, − TrwB, − MCM, , and RepA or RuvB, − all of which have a channel diameter of 1–2 nm . Revolving motors include the DNA translocases Ftsk in Gram-negative bacteria, SpoIIIE or SftA (YtpS) in Gram-positive bacteria, A32 ATPase of poxvirus, − DNA packaging enzyme of adenovirus, − the genome segregation enzymes of mimivirus, ,− as well as the DNA packaging motors of herpesvirus, − SPP1, T7, HK97, P22, and Phi29 . The three classes of biomotors differ in structure and function, but utilize similar mechanisms for force generation to perform mechanical work.…”

mentioning

confidence: 99%

Controlling the Revolving and Rotating Motion Direction of Asymmetric Hexameric Nanomotor by Arginine Finger and Channel Chirality

et al. 2019

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Nanomotors in nanotechnology are as important as engines in daily life. Many ATPases are nanoscale biomotors classified into three categories based on the motion mechanisms in transporting substrates: linear, rotating, and the recently discovered revolving motion. Most biomotors adopt a multisubunit ring-shaped structure that hydrolyzes ATP to generate force. How these biomotors control the motion direction and regulate the sequential action of their multiple subunits is intriguing. Many ATPases are hexameric with each monomer containing a conserved arginine finger. This review focuses on recent findings on how the arginine finger controls motion direction and coordinates adjacent subunit interactions in both revolving and rotating biomotors. Mechanisms of intersubunit interactions and sequential movements of individual subunits are evidenced by the asymmetrical appearance of one dimer and four monomers in high-resolution structural complexes. The arginine finger is situated at the interface of two subunits and extends into the ATP binding pocket of the downstream subunit. An arginine finger mutation results in deficiency in ATP binding/hydrolysis, substrate binding, and transport, highlighting the importance of the arginine finger in regulating energy transduction and motor function. Additionally, the roles of channel chirality and channel size are discussed as related to controlling one-way trafficking and differentiating the revolving and rotating mechanisms. Finally, the review concludes by discussing the conformational changes and entropy conversion triggered by ATP binding/hydrolysis, offering a view different from the traditional concept of ATP-mediated mechanochemical energy coupling. The elucidation of the motion mechanism and direction control in ATPases could facilitate nanomotor fabrication in nanotechnology.

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Identification of the Epstein Barr Virus portal

Cited by 9 publications

References 55 publications

The Portal Vertex of KSHV Promotes Docking of Capsids at the Nuclear Pores

The Portal Vertex of KSHV Promotes Docking of Capsids at the Nuclear Pores

Identifying the Cellular Interactome of Epstein-Barr Virus Lytic Regulator Zta Reveals Cellular Targets Contributing to Viral Replication

Controlling the Revolving and Rotating Motion Direction of Asymmetric Hexameric Nanomotor by Arginine Finger and Channel Chirality

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