Host cell dependence of viral morphology

Roberts, Paul C.; Compans, Richard W.

doi:10.1073/pnas.95.10.5746

Cited by 121 publications

(127 citation statements)

References 39 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.

219

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.

219

280

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“…Previous studies have shown that cytochalasin D has an effect on viral internalization, assembly, and budding of influenza A virus in a virus strain-and cell polarity-dependent manner (31)(32)(33). Therefore, we first examined the effect of cytochalasin D on the expression of influenza proteins.…”

Section: An Intact Actin Cytoskeleton Is Essential For Full Expressiomentioning

confidence: 99%

Actin and RIG-I/MAVS Signaling Components Translocate to Mitochondria upon Influenza A Virus Infection of Human Primary Macrophages

Öhman

Rintahaka

Kalkkinen

et al. 2009

The Journal of Immunology

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Influenza A virus is one of the most important causes of respiratory infection. During viral infection, multiple cell signaling cascades are activated, resulting in the production of antiviral cytokines and initiation of programmed cell death of virus-infected cells. In the present study, we have used subcellular proteomics to reveal the host response to influenza A infection at the protein level in human macrophages. Macrophages were infected with influenza A virus, after which the cytosolic and mitochondrial cell fractions were prepared and analyzed by using two-dimensional electrophoresis for protein separation and mass spectrometry for protein identification. In cytosolic proteomes, the level of several heat shock proteins and fragments of cytoskeletal proteins was clearly up-regulated during influenza A virus infection. In mitochondrial proteomes, simultaneously with the expression of viral proteins, the level of intact actin and tubulin was highly up-regulated. This was followed by translocation of the components of antiviral RNA recognition machinery, including RIG-I (retinoic acid-inducible protein I), TRADD (TNFR1-associated death domain protein), TRIM25 (tripartite motif protein 25), and IKKε (inducible IκB kinase), onto the mitochondria. Cytochalasin D, a potent inhibitor of actin polymerization, clearly inhibited influenza A virus-induced expression of IFN-β, IL-29, and TNF-α, suggesting that intact actin cytoskeleton structure is crucial for proper activation of antiviral response. At late phases of infection mitochondrial fragmentation of actin was seen, indicating that actin fragments, fractins, are involved in disruption of mitochondrial membranes during apoptosis of virus-infected cells. In conclusion, our results suggest that actin network interacts with mitochondria to regulate both antiviral and cell death signals during influenza A virus infection.

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“…The surfaces of infected cells are covered by large clumps of filamentous protrusions, which can be visualized by light microscopy, immunofluorescence staining, and electron microscopy (2, 3, 35, 51). The morphology of budding virions depends on cellular determinants such as polarized cell phenotype and the integrity of the actin microfilament network (6,39). The determinants of RSV's spherical and filamentous morphological forms and the roles of such particles in virus transmission and pathogenicity are not clearly defined.…”

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confidence: 99%

RhoA Signaling Is Required for Respiratory Syncytial Virus-Induced Syncytium Formation and Filamentous Virion Morphology

Gower

Pastey

Peeples

et al. 2005

J Virol

112

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Respiratory syncytial virus (RSV) is an important human pathogen that can cause severe and life-threatening respiratory infections in infants, the elderly, and immunocompromised adults. RSV infection of HEp-2 cells induces the activation of RhoA, a small GTPase. We therefore asked whether RhoA signaling is important for RSV replication or syncytium formation. The treatment of HEp-2 cells with Clostridium botulinum C3, an enzyme that ADP-ribosylates and specifically inactivates RhoA, inhibited RSV-induced syncytium formation and cell-to-cell fusion, although similar levels of PFU were released into the medium and viral protein expression levels were equivalent. Treatment with another inhibitor of RhoA signaling, the Rho kinase inhibitor Y-27632, yielded similar results. Scanning electron microscopy of C3-treated infected cells showed reduced numbers of single blunted filaments, in contrast to the large clumps of long filaments in untreated infected cells. These data suggest that RhoA signaling is associated with filamentous virus morphology, cell-to-cell fusion, and syncytium formation but is dispensable for the efficient infection and production of infectious virus in vitro. Next, we developed a semiquantitative method to measure spherical and filamentous virus particles by using sucrose gradient velocity sedimentation. Fluorescence and transmission electron microscopy confirmed the separation of spherical and filamentous forms of infectious virus into two identifiable peaks. The C3 treatment of RSV-infected cells resulted in a shift to relatively more spherical virions than those from untreated cells. These data suggest that viral filamentous protuberances characteristic of RSV infection are associated with RhoA signaling, are important for filamentous virion morphology, and may play a role in initiating cell-to-cell fusion.

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Host cell dependence of viral morphology

Cited by 121 publications

References 39 publications

Structural organization of a filamentous influenza A virus

Structural organization of a filamentous influenza A virus

Actin and RIG-I/MAVS Signaling Components Translocate to Mitochondria upon Influenza A Virus Infection of Human Primary Macrophages

RhoA Signaling Is Required for Respiratory Syncytial Virus-Induced Syncytium Formation and Filamentous Virion Morphology

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