Vaccinia Virus Motility

Smith, Geoffrey L.; Murphy, Brendan; Law, Mansun

doi:10.1146/annurev.micro.57.030502.091037

Cited by 105 publications

(88 citation statements)

References 125 publications

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“…F12 is not predicted to contain a transmembrane domain; therefore, its method of association with IEV was unclear. Furthermore, a recent review suggested that two putative myristoylation sites in F12 may be responsible for anchoring it to the outer membrane of IEV (14). The results from our alkaline carbonate extraction and Triton X-114 partitioning experiments suggest that F12 interacts with IEV through a peripheral association and not an integral association, such as through an unidentified transmembrane domain or protein lipidation.…”

Section: Discussionmentioning

confidence: 66%

Vaccinia Virus Protein F12 Associates with Intracellular Enveloped Virions through an Interaction with A36

Johnston

Ward

2009

J Virol

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Vaccinia virus is the prototypical member of the family Poxviridae. Three morphologically distinct forms are produced during infection: intracellular mature virions (IMV), intracellular enveloped virions (IEV), and extracellular enveloped virions (EEV). Two viral proteins, F12 and A36, are found exclusively on IEV but not on IMV and EEV. Analysis of membranes from infected cells showed that F12 was only associated with membranes and is not an integral membrane protein. A yeast two-hybrid assay revealed an interaction between amino acids 351 to 458 of F12 and amino acids 91 to 111 of A36. We generated a recombinant vaccinia virus that expresses an F12, which lacks residues 351 to 458. Characterization of this recombinant revealed a small-plaque phenotype and a subsequent defect in virus release similar to a recombinant virus that had F12L deleted. In addition, F12 lacking residues 351 to 458 was unable to associate with membranes in infected cells. These results suggest that F12 associates with IEV through an interaction with A36 and that this interaction is critical for the function of F12 during viral egress.Vaccinia virus (VV) is a member of the Poxviridae family of viruses and replicates entirely in the cytoplasm of infected cells. During morphogenesis, the first infectious forms produced are called intracellular mature virions (IMV) (8,12). A subset of IMV are transported along microtubules to the site of wrapping at the trans-Golgi network (6, 11) and early endosome (17), where they acquire two additional membranes and are termed intracellular enveloped virions (IEV). IEV are transported along microtubules to the cell periphery, where their outermost membrane fuses with the plasma membrane, releasing infectious virions onto the cell surface (9, 13). Surface-associated viral particles are termed cellassociated enveloped virions (CEV). Actin tails polymerized beneath CEV propel virions away from infected cells and toward adjacent cells, helping to facilitate cell-to-cell spread (7,21). Some virions are released from the cell surface and are termed extracellular enveloped virions (EEV), which are involved in longrange virus dissemination (10).There are seven known, IEV-specific, viral proteins: A33, A34, A36, A56, B5, F12, and F13 (reviewed by Smith et al. [15]). F12 and A36 are found exclusively on the outermost envelope of IEV and are not associated with CEV and EEV (18,24). A36 has been reported to be involved in the transport of virions to the cell surface via an interaction with the molecular motor kinesin (20), as well as actin tail formation beneath CEV (5). F12 is a 65-kDa protein that is expressed predominantly late during infection (25). Deletion of the gene causes a small plaque phenotype on cell monolayers, indicating that F12 has a role in infectious enveloped virion production and/or release (13, 25). F12 is not predicted to contain a signal sequence or a transmembrane domain, and its method of association with the outermost IEV membrane is unknown. In this report, we show that F12 is associate...

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Section: Discussionmentioning

confidence: 66%

Vaccinia Virus Protein F12 Associates with Intracellular Enveloped Virions through an Interaction with A36

Johnston

Ward

2009

J Virol

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“…The reduction in latent virus with the 27 ploitation of normal cellular functions then allows more efficient virion dissemination than simple diffusion. Such mechanisms are well defined for poxviruses, which use actin polymerization to extend long, virion-laden processes from infected cells (24). MHV-68 infection also induces cellular processes, particularly on macrophages (P. G. Stevenson, unpublished data), and the presence of gp48 on small processes extending from infected MEFs (Fig.…”

Section: Discussionmentioning

confidence: 90%

The Murine Gammaherpesvirus 68 ORF27 Gene Product Contributes to Intercellular Viral Spread

May

Walker

Colaco

et al. 2005

J Virol

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Herpesviruses remain predominantly cell associated within their hosts, implying that they spread between cells by a mechanism distinct from free virion release. We previously identified the efficient release of murine gammaherpesvirus 68 (MHV-68) virions as a function of the viral gp150 protein. Here we show that the MHV-68 ORF27 gene product, gp48, contributes to the direct spread of viruses from lytically infected to uninfected cells. Monoclonal antibodies to gp48 identified it on infected cell surfaces and in virions. gp48-deficient viruses showed no obvious deficit in virion cell binding, single-cycle replication, or virion release but had reduced lytic propagation between cells. After intranasal infection of mice, ORF27-deficient viruses were impaired predominantly in lytic replication in the lungs. There was a small deficit in latency establishment, but long-term latency appeared normal. Since ORF27 has homologs in both Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, it is likely part of a conserved mechanism employed by gammaherpesviruses to disseminate lytically in their hosts.Epidemic viruses generally rely on high infectivities to transmit infection before immune responses become effective. In contrast, persistent viruses use immune evasion to establish a state of chronic, low-level infectivity. In keeping with this strategy of stealth, persistent viruses generally release virions only in very specific settings and otherwise spread via cell-cell contact.Herpesviruses are archetypal persistent pathogens. Acute infections are not associated with a detectable viremia, consistent with a predominance of direct, cell-to-cell virus transfer. In herpes simplex virus, this is a function of gE and gI, which are dispensable for lytic replication in vitro but contribute to dissemination in vivo (11). Glycoprotein D of pseudorabies virus, which binds virions to cells, illustrates the converse: it is important for growth in vitro but dispensable for growth in vivo (22). Thus, spread by virion release and spread by cell-cell contact, though clearly overlapping in their requirements for membrane fusion, appear to be separable processes involving distinct attachment proteins. Any therapeutic intervention must therefore encompass these two separate modes of viral spread.We are interested in the molecular processes that underlie the dissemination of gammaherpesviruses. These viruses lack genetic homologs of alphaherpesvirus gE and gI. The virusdriven proliferation of latently infected lymphocytes plays a central role in host colonization by gammaherpesviruses (8), but lytic replication must still be required for entry into and exit from hosts as well as for viral transit between different cell types. Cell-binding virion proteins have been identified for Epstein-Barr virus (EBV) (6, 32) and Kaposi's sarcoma-associated herpesvirus (KSHV) (2), but the processes by which gammaherpesviruses spread between cells in vivo remain unknown. Moreover, the strict species tropisms of EBV and KSHV make it difficult to u...

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“…Intracellular enveloped Vaccinia virus particles move from their perinuclear assembly site to the plasma membrane along microtubules [58][59][60][61][62][63] . These particles fuse with the plasma membrane, but remain attached as cell-associated enveloped virus (CEV) 64 . The envelope protein B5R activates the Src family kinases, which phosphorylate another viral protein A36R, which in turn recruits the actin polymerization machinery, forming a characteristic actin tail beneath the CEV to enhance cell-to-cell spread of the virus 65 (FIG.…”

Section: Viral Assembly and Egressmentioning

confidence: 99%

Virus trafficking – learning from single-virus tracking

2007

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What could be a better way to study virus trafficking than 'miniaturizing oneself' and 'taking a ride with the virus particle' on its journey into the cell? Single-virus tracking in living cells potentially provides us with the means to visualize the virus journey. This approach allows us to follow the fate of individual virus particles and monitor dynamic interactions between viruses and cellular structures, revealing previously unobservable infection steps. The entry, trafficking and egress mechanisms of various animal viruses have been elucidated using this method. The combination of single-virus trafficking with systems approaches and state-of-the-art imaging technologies should prove exciting in the future.

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Vaccinia Virus Motility

Cited by 105 publications

References 125 publications

Vaccinia Virus Protein F12 Associates with Intracellular Enveloped Virions through an Interaction with A36

Vaccinia Virus Protein F12 Associates with Intracellular Enveloped Virions through an Interaction with A36

The Murine Gammaherpesvirus 68 ORF27 Gene Product Contributes to Intercellular Viral Spread

Virus trafficking – learning from single-virus tracking

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