Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells

Villa, Nancy Y.; Bartee, Eric; Mohamed, Mohamed R.; Rahman, Masmudur M.; Barrett, John W.; McFadden, Grant

doi:10.1016/j.virol.2010.02.027

Cited by 25 publications

(20 citation statements)

References 60 publications

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“…Despite their similarities as members of the poxvirus family, the two viruses exhibit very divergent host tropisms, and they can differ dramatically in terms of which specific human cancer cells are permissive for infection and oncolysis (32). Although most poxviruses bind to a wide spectrum of mammalian cells in culture (15), there is growing evidence that the initial binding/entry step can be quite different among poxviruses (43,44).…”

Section: Discussionmentioning

confidence: 99%

“…However, the tropism of these two poxviruses can be quite different for many human cancer cells (32), and detailed studies comparing the attachment of MYXV and VACV virions to target cells have not yet been conducted. To directly test the binding of MYXV and VACV to different cell types and under different conditions, we have constructed fluorescently tagged versions of MYXV and VACV and then compared the binding and infection of these viruses to various human normal and cancerous cells.…”

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confidence: 99%

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Myxoma and Vaccinia Viruses Bind Differentially to Human Leukocytes

Chan

Bartee²,

Moreb

et al. 2013

J Virol

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Myxoma and Vaccinia Viruses Bind Differentially to Human Leukocytes

Chan

Bartee²,

Moreb

et al. 2013

J Virol

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“…[8][9][10] MYXV is a viral oncolytic agent that is nonpathogenic to humans and mice but has natural tropism for a variety of human cancers. [11][12][13] In the course of developing MYXV as an ex vivo purging agent for transplant, we serendipitously discovered that NSG mice receiving human HCT xenografts treated ex vivo with MYXV developed no GVHD, lived longer, and yet still exhibited robust human hematopoietic engraftment in the recipient bone marrow. 14 We hypothesized that MYXV impaired the GVHD capacity of alloreactive donor T lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

Myxoma virus suppresses proliferation of activated T lymphocytes yet permits oncolytic virus transfer to cancer cells

Villa¹,

Wasserfall²,

Meacham³

et al. 2015

Blood

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“…It has also been reported that MYXV differs in some ways from VACV with regard to the mechanisms of cell entry. For example, MYXV entry is not stimulated by acid pH (57), an observation that may be related to the fact that MYXV does not encode an obvious homolog of the VACV A26 acidsensitive fusion suppressor protein. Of course, A26L is not the only VACV gene involved in promoting poxvirus entry and exit, which is missing from MYXV.…”

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confidence: 99%

Modulation of the Myxoma Virus Plaque Phenotype by Vaccinia Virus Protein F11

Irwin

Evans

2012

J Virol

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Vaccinia virus (VACV) produces large plaques consisting of a rapidly expanding ring of infected cells surrounding a lytic core, whereas myxoma virus (MYXV) produces small plaques that resemble a focus of transformed cells. This is odd, because bioinformatics suggests that MYXV carries homologs of nearly all of the genes regulating Orthopoxvirus attachment, entry, and exit. So why does MYXV produce foci? One notable difference is that MYXV-infected cells produce few of the actin microfilaments that promote VACV exit and spread. This suggested that although MYXV carries homologs of the required genes (A33R, A34R, A36R, and B5R), they are dysfunctional. To test this, we produced MYXV recombinants expressing these genes, but we could not enhance actin projectile formation even in cells expressing all four VACV proteins. Another notable difference between these viruses is that MYXV lacks a homolog of the F11L gene. F11 inhibits the RhoA-mDia signaling that maintains the integrity of the cortical actin layer. We constructed an MYXV strain encoding F11L and observed that, unlike wild-type MYXV, the recombinant virus disrupted actin stress fibers and produced plaques up to 4-fold larger than those of controls, and these plaques expanded ϳ6-fold faster. These viruses also grew to higher titers in multistep growth conditions, produced higher levels of actin projectiles, and promoted infected cell movement, although neither process was to the extent of that observed in VACV-infected cells. Thus, one reason for why MYXV produces small plaques is that it cannot spread via actin filaments, although the reason for this deficiency remains obscure. A second reason is that leporipoxviruses lack vaccinia's capacity to disrupt cortical actin. P oxviruses produce two kinds of plaques in culture. The first kind is formed rapidly by viruses like vaccinia virus (VACV), and typically they comprise a ring of infected cells surrounding a large central clearing or lytic zone. The second type of poxvirus plaque is smaller, grows slower, and consists of a clump of virusinfected cells. These plaques look more like a cluster of transformed cells and are sometimes called foci. Such plaques are produced by tumorigenic poxviruses like the leporipoxviruses myxoma virus (MYXV) and Shope fibroma virus. Although it is well established that the appearance of poxvirus plaques is determined by the genetics of both the host and the virus, why MYXV plaques look so different from VACV plaques, even when plated on the same cell type, is not well understood.The process of plaque formation depends (in part) upon how well viruses can engage the host machinery to spread efficiently from cell to cell, processes that are best understood for VACV (reviewed in references 44, 51, and 58). VACV characteristically produces several different forms of infectious virus. Mature viruses (MV) are bounded by just a single lipid bilayer. MV comprise the most abundant infectious form and are probably released by cell lysis. However, some MV migrate away from viral factories, w...

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Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells

Cited by 25 publications

References 60 publications

Myxoma and Vaccinia Viruses Bind Differentially to Human Leukocytes

Myxoma and Vaccinia Viruses Bind Differentially to Human Leukocytes

Myxoma virus suppresses proliferation of activated T lymphocytes yet permits oncolytic virus transfer to cancer cells

Modulation of the Myxoma Virus Plaque Phenotype by Vaccinia Virus Protein F11

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