Vaccinia virus intracellular enveloped virions move to the cell periphery on microtubules in the absence of the A36R protein

Herrero-Martinez, Esteban; Roberts, Kim L.; Hollinshead, Michael; Smith, Geoffrey L.

doi:10.1099/vir.0.81260-0

Cited by 40 publications

(74 citation statements)

References 29 publications

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“…Suggesting that MDAs may have virus-specific effects, we and others have observed that, while they enhance rhabdoviruses, microtubule destabilizers robustly inhibit vaccinia growth 36 . However, other viruses have been reported to grow at least equivalently in cells with destabilized microtubules.…”

Section: Discussionmentioning

confidence: 99%

Microtubule disruption synergizes with oncolytic virotherapy by inhibiting interferon translation and potentiating bystander killing

et al. 2015

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In this study, we show that several microtubule-destabilizing agents used for decades for treatment of cancer and other diseases also sensitize cancer cells to oncolytic rhabdoviruses and improve therapeutic outcomes in resistant murine cancer models. Drug-induced microtubule destabilization leads to superior viral spread in cancer cells by disrupting type I IFN mRNA translation, leading to decreased IFN protein expression and secretion. Furthermore, microtubule-destabilizing agents specifically promote cancer cell death following stimulation by a subset of infection-induced cytokines, thereby increasing viral bystander effects. This study reveals a previously unappreciated role for microtubule structures in the regulation of the innate cellular antiviral response and demonstrates that unexpected combinations of approved chemotherapeutics and biological agents can lead to improved therapeutic outcomes.

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Section: Discussionmentioning

confidence: 99%

Microtubule disruption synergizes with oncolytic virotherapy by inhibiting interferon translation and potentiating bystander killing

et al. 2015

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“…For vaccinia virus and African swine fever virus (DNA viruses), both microtubule-dependent transport and actin-based motility are used to drive viral particles (36)(37)(38). Intracellular vaccinia virus particles are transported along microtubules with speeds of 500-750 nm/s (35,39). The actin-based propelling of extracellular vaccinia virus particles takes place with velocities of ∼170 nm/s (36).…”

Section: Discussionmentioning

confidence: 99%

Live-cell imaging of Marburg virus-infected cells uncovers actin-dependent transport of nucleocapsids over long distances

Schudt

Kolesnikova

Dolnik

et al. 2013

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

122

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Transport of large viral nucleocapsids from replication centers to assembly sites requires contributions from the host cytoskeleton via cellular adaptor and motor proteins. For the Marburg and Ebola viruses, related viruses that cause severe hemorrhagic fevers, the mechanism of nucleocapsid transport remains poorly understood. Here we developed and used live-cell imaging of fluorescently labeled viral and host proteins to characterize the dynamics and molecular requirements of nucleocapsid transport in Marburg virus-infected cells under biosafety level 4 conditions. The study showed a complex actin-based transport of nucleocapsids over long distances from the viral replication centers to the budding sites. Only after the nucleocapsids had associated with the matrix viral protein VP40 at the plasma membrane were they recruited into filopodia and cotransported with host motor myosin 10 toward the budding sites at the tip or side of the long cellular protrusions. Three different transport modes and velocities were identified: (i) Along actin filaments in the cytosol, nucleocapsids were transported at ∼200 nm/s; (ii) nucleocapsids migrated from one actin filament to another at ∼400 nm/s; and (iii) VP40-associated nucleocapsids moved inside filopodia at 100 nm/s. Unique insights into the spatiotemporal dynamics of nucleocapsids and their interaction with the cytoskeleton and motor proteins can lead to novel classes of antivirals that interfere with the trafficking and subsequent release of the Marburg virus from infected cells.dual-color imaging | reverse genetics | viral inclusion bodies T he filoviruses Marburg (MARV) and Ebola (EBOV) cause severe hemorrhagic fever with high-case-fatality rates in humans and nonhuman primates (1-3). Although the interplay of filoviral proteins leading to the transcription and replication of the viral genome and the formation of the viral nucleocapsids (NCs) is rather well understood, we are only just beginning to unravel the complex interactions between the viral and cellular proteins that are necessary to transport the NCs from the sites of their formation to the budding sites. The central protein within the NC is the nucleoprotein NP, which forms complexes with VP35, VP30, and VP24 (4, 5). The helical MARV NC is composed of the RNAdependent RNA polymerase (L), the polymerase cofactor VP35, the viral proteins VP30 and VP24, and NP, which encapsidates the viral genome (5-7). Within the viral particle, the NC is surrounded by a regular lattice of the matrix protein VP40 (5, 8, 9). The outside of the VP40 lattice contacts the viral envelope, in which the glycoprotein GP is inserted (10).MARV virogenesis begins with the formation of perinuclear inclusions which, analogous to the EBOV, are considered to be sites of viral replication and the assembly of new NCs (8, 9, 11). Later in the replication cycle, NCs are detected in the cytosol, at the plasma membrane, and in filopodia, the preferred sites of MARV budding (12, 13). The glycoprotein GP reaches the plasma membrane via vesicular se...

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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 .…”

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 intracellular enveloped virions move to the cell periphery on microtubules in the absence of the A36R protein

Cited by 40 publications

References 29 publications

Microtubule disruption synergizes with oncolytic virotherapy by inhibiting interferon translation and potentiating bystander killing

Microtubule disruption synergizes with oncolytic virotherapy by inhibiting interferon translation and potentiating bystander killing

Live-cell imaging of Marburg virus-infected cells uncovers actin-dependent transport of nucleocapsids over long distances

Virus trafficking – learning from single-virus tracking

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