Budding of filamentous and non-filamentous influenza A virus occurs via a VPS4 and VPS28-independent pathway

Bruce, Emily A.; Medcalf, Liz; Crump, Colin M.; Noton, Sarah L.; Stuart, Amanda D.; Wise, Helen; Elton, Debra; Bowers, Katherine; Digard, Paul

doi:10.1016/j.virol.2009.05.016

Cited by 53 publications

(65 citation statements)

References 59 publications

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“…Cellular factors associated with the vacuolar sorting pathway are implicated in virus budding and release for several virus families, and some of these may form protein assemblies that regulate the physical constriction required for pinching-off (38). It is not known what host factors regulate orthomyxovirus budding (39,40), but host factors such as actin and the virus M2 protein may contribute to the filamentous phenotype (20,41,42).…”

Section: Discussionmentioning

confidence: 99%

Structural organization of a filamentous influenza A virus

Calder

Wasilewski²,

Berriman³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

207

280

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Influenza is a lipid-enveloped, pleomorphic virus. We combine electron cryotomography and analysis of images of frozen-hydrated virions to determine the structural organization of filamentous influenza A virus. Influenza A/Udorn/72 virions are capsule-shaped or filamentous particles of highly uniform diameter. We show that the matrix layer adjacent to the membrane is an ordered helix of the M1 protein and its close interaction with the surrounding envelope determines virion morphology. The ribonucleoprotein particles (RNPs) that package the genome segments form a tapered assembly at one end of the virus interior. The neuraminidase, which is present in smaller numbers than the hemagglutinin, clusters in patches and are typically present at the end of the virion opposite to RNP attachment. Incubation of virus at low pH causes a loss of filamentous morphology, during which we observe a structural transition of the matrix layer from its helical, membrane-associated form to a multilayered coil structure inside the virus particle. The polar organization of the virus provides a model for assembly of the virion during budding at the host membrane. Images and tomograms of A/Aichi/68 X-31 virions show the generality of these conclusions to non-filamentous virions.electron cryomicroscopy | matrix protein | ribonucleoprotein particles hemagglutinin | neuramindase

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Section: Discussionmentioning

confidence: 99%

Structural organization of a filamentous influenza A virus

Calder

Wasilewski²,

Berriman³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

207

280

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“…However, the observation that transient expression of the DN Vps4 mutant did not affect production of either influenza virus (Bruce et al, 2009) or respiratory syncytial virus (Utley et al, 2008), whereas it had a marked effect on production of HSV-1 particles (Crump et al, 2007), argues against this explanation. The latter observations suggest that expression of this protein, although undoubtedly detrimental to cell function, does not result in gross perturbation of endosome formation to the extent that all enveloped virus production is impaired.…”

Section: Discussionmentioning

confidence: 99%

Vps4 and the ESCRT-III complex are required for the release of infectious hepatitis C virus particles

Corless

Crump

Griffin

et al. 2009

Journal of General Virology

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The mechanisms by which infectious hepatitis C virus (HCV) particles are assembled and released from infected cells remain poorly characterized. In this regard, many other enveloped viruses, notably human immunodeficiency virus type 1, have been shown to utilize the host vacuolar protein sorting machinery (also known as the endosomal sorting complex required for transport; ESCRT) to traffic through the cell and effect the membrane rearrangements required for the formation of enveloped particles. We postulated that this might also apply to HCV. To test this hypothesis, we established a method of conditional virus-like particle assembly involving transcomplementation of an envelope-deleted JFH-1 genome using plasmid transfection. This system reliably produced virus particles that were infectious and could be enumerated easily by focusforming assay in Huh7 cells. Following co-transfection with plasmids expressing various dominant-negative forms of either components of the ESCRT-III complex or Vps4 (the AAA ATPase that recycles the ESCRT complexes), a reduction in particle production was seen. No significant effect was observed after co-transfection of dominant-negative ESCRT-I or Alix, an ESCRT associated protein. Dominant-negative Vps4 or ESCRT-III components had no effect on either virus genome replication or the accumulation of intracellular infectious particles. These data were confirmed using cell culture infectious HCV and we conclude that HCV requires late components of the ESCRT pathway for release of infectious virus particles. INTRODUCTIONHepatitis C virus (HCV) represents a major global health burden. An estimated 170 million people are chronically infected worldwide and a significant proportion of these will go on to develop end stage liver disease. Current drug treatments are poorly tolerated and are only effective in approximately 50 % of individuals. There is, therefore, a pressing need for a greater understanding of the molecular mechanisms involved in HCV infection in order for novel drug targets to be identified.HCV is the prototype member of the genus Hepacivirus in the family Flaviviridae. It is a single-stranded, positive-sense RNA virus whose genome encodes a single ORF. This is translated in a cap-independent manner from an internal ribosome entry site (IRES) located in the 59 untranslated region, into a single polyprotein of approximately 3000 aa. The polyprotein is proteolytically cleaved by host and viral proteases to form 10 mature proteins; the structural proteins (core, E1 and E2), a viroporin p7 and the non-structural proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B).Although recent advances in the development of tissue culture systems for the study of the HCV life cycle (Lindenbach et al., 2005;Wakita et al., 2005;Zhong et al., 2005) have defined a critical role for lipid droplets in virus assembly (Miyanari et al., 2007), the precise mechanism by which infectious HCV particles are assembled and released remains poorly characterized. In particular, it has not been established how nascent...

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“…ATP is required for influenza virus budding (18), and some viruses such as HIV and Ebola virus use the host AAAtype ATPase Vps4 for virion budding from cells (19,20). However, influenza virus budding does not depend on Vps4 (21,22). These observations suggest that F1β at the plasma membrane could be an ATPase required for influenza virus budding.…”

Section: Virion Formation/budding Of Influenza Virus Particles Is Redmentioning

confidence: 97%

F1Fo-ATPase, F-type proton-translocating ATPase, at the plasma membrane is critical for efficient influenza virus budding

Gorai¹,

Goto²,

Noda

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The identification of host factors involved in virus replication is important to understand virus life cycles better. Accordingly, we sought host factors that interact with the influenza viral nonstructural protein 2 by using coimmunoprecipitation followed by mass spectrometry. Among proteins associating with nonstructural protein 2, we focused on the β subunit of the F1Fo-ATPase, which received a high probability score in our mass spectrometry analysis. The siRNA-mediated down-regulation of the β subunit of the F1Fo-ATPase reduced influenza virion formation and virus growth in cell culture. We further found that efficient influenza virion formation requires the ATPase activity of F1Fo-ATPase and that plasma membrane-associated, but not mitochondrial, F1Fo-ATPase is important for influenza virion formation and budding. Hence, our data identify plasma membrane-associated F1Fo-ATPase as a critical host factor for efficient influenza virus replication.

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Budding of filamentous and non-filamentous influenza A virus occurs via a VPS4 and VPS28-independent pathway

Cited by 53 publications

References 59 publications

Structural organization of a filamentous influenza A virus

Structural organization of a filamentous influenza A virus

Vps4 and the ESCRT-III complex are required for the release of infectious hepatitis C virus particles

F1Fo-ATPase, F-type proton-translocating ATPase, at the plasma membrane is critical for efficient influenza virus budding

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