Mechanisms of Apoptosis During Reovirus Infection

Clarke, Penny; Richardson-Burns, Sarah M.; DeBiasi, Roberta L.; Tyler, Kenneth L.

doi:10.1007/3-540-27320-4_1

Cited by 34 publications

(33 citation statements)

References 50 publications

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“…IRF1/ 5-responsive genes include caspase-1 and tumor necrosis factor superfamily member 10, also known as TRAIL (20,59,67), which were also upregulated in the spinal cords of reovirus-infected mice. Apoptosis is triggered in the SC following reovirus infection and is important for reovirus-induced disease (4,5,15,30). Further, extrinsic apoptotic signaling is activated following infection of primary cortical neurons and during reovirus encephalitis, and it is required for neuronal cell death in vitro (14,63).…”

Section: Discussionmentioning

confidence: 99%

Activation of Innate Immune Responses in the Central Nervous System during Reovirus Myelitis

Schittone

Dionne²,

Tyler³

et al. 2012

J Virol

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f Reovirus infection of the murine spinal cord (SC) was used as a model system to investigate innate immune responses during viral myelitis, including the activation of glia (microglia and astrocytes) and interferon (IFN) signaling and increased expression of inflammatory mediators. Reovirus myelitis was associated with the pronounced activation of SC glia, as evidenced by characteristic changes in cellular morphology and increased expression of astrocyte and microglia-specific proteins. Expression of inflammatory mediators known to be released by activated glia, including interleukin-1␤ (IL-1␤), tumor necrosis factor alpha (TNF-␣), chemokine (C-C motif) ligand 5 (CCL 5), chemokine (C-X-C motif) ligand 10 (CXCL10), and gamma interferon (IFN-␥), was also significantly upregulated in the SC of reovirus-infected animals compared to mock-infected controls. Reovirus infection of the mouse SC was also associated with increased expression of genes involved in IFN signaling, including IFN-stimulated genes (ISG). Further, reovirus infection of mice deficient in the expression of the IFN-␣/␤ receptor (IFNAR ؊/؊ ) resulted in accelerated mortality, demonstrating that IFN signaling is protective during reovirus myelitis. Experiments performed in ex vivo SC slice cultures (SCSC) confirmed that resident SC cells contribute to the production of at least some of these inflammatory mediators and ISG during reovirus infection. Microglia, but not astrocytes, were still activated, and glia-associated inflammatory mediators were still produced in reovirus-infected INFAR ؊/؊ mice, demonstrating that IFN signaling is not absolutely required for these neuroinflammatory responses. Our results suggest that activated glia and inflammatory mediators contribute to a local microenvironment that is deleterious to neuronal survival.

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Section: Discussionmentioning

confidence: 99%

Activation of Innate Immune Responses in the Central Nervous System during Reovirus Myelitis

Schittone

Dionne²,

Tyler³

et al. 2012

J Virol

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“…However, there is limited knowledge of expression pattern of Bax in response to dsRNA viruses, and the specific role of Bax during the virus-induced apoptosis in teleost fish is still unclear. In addition, given that apoptosis can affect pathogenesis and accelerate the replication of virus, identification of a Bax-dependent apoptotic pathway in grass carp after GCRV infection might be a viable way to develop a virus resistance strategy for breeding of grass carp (Clarke et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Cloning and characterization of Bax1 and Bax2 genes of Ctenopharyngodon idellus and evaluation of transcript expression in response to grass carp reovirus infection

Wang

Pei

et al. 2016

Fish Physiol Biochem

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Multidomain proapoptotic Bcl-2-associated X (Bax) protein is an essential effector responsible for mitochondrial outer membrane permeabilization, resulting in cell death via apoptosis. In this study, two Bax genes of grass carp (Ctenopharyngodon idellus), designated as CiBax1 and CiBax2, were isolated and analyzed. The obtained CiBax1 cDNA is 2058 bp long, with a 579 bp open reading frame (ORF) coding a protein of 192 amino acid residues. The full-length cDNA of CiBax2 is 1161 bp, with a 618 bp ORF coding 205 amino acids. Both CiBax1 and CiBax2 are typical members of Bcl-2 family containing conserved Bcl and C-terminal domains, and they share conserved synteny with zebrafish Bax genes despite the grass carp Bax mapping to different linkage groups. Phylogenetic analysis showed that CiBax1 was clustered with Bax from most teleost fish, and CiBax2 was close to Bax2 from teleost fish but far separated from that of Salmo salar. Quantitative real-time PCR analysis revealed broad expression of CiBax1 and CiBax2 in tissues from healthy grass carp, but the relative expression level differed. The mRNA expression of CiBax1 and CiBax2 was both upregulated significantly and peaked in all examined tissues at days 5 or 6 post-infection with grass carp reovirus. Subcellular localization indicated that CiBax1 protein was localized in both nucleus and cytosol, while CiBax2 protein only in cytosol. Moreover, CiBax2, but not CiBax1 was colocalized with mitochondrion under normal condition. Taken together, the findings would be helpful for further understanding of the function of Bax in teleost fish.

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“…These viruses are generally cytolytic as they kill and lyse infected cells in culture; this has been generally attributed to apoptosis (reviewed in: Clarke et al, 2005;Danthi et al, 2010), although both necrotic (Berger and Danthi, 2013) and autophagic (Thirukkumaran et al, 2013) cell death likely occurs in certain cell types.…”

Section: Introductionmentioning

confidence: 99%

Amino acids substitutions in σ1 and μ1 outer capsid proteins of a Vero cell-adapted mammalian orthoreovirus are required for optimal virus binding and disassembly

Sandekian

Lemay

2015

Virus Research

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In a recent study, the serotype 3 Dearing strain of mammalian orthoreovirus was adapted to Vero cells; cells that exhibit a limited ability to support the early steps of reovirus uncoating and are unable to produce interferon as an antiviral response upon infection. The Vero cell-adapted virus (VeroAV) exhibits amino acids substitutions in both the σ1 and μ1 outer capsid proteins but no changes in the σ3 protein. Accordingly, the virus was shown not to behave as a classical uncoating mutant.In the present study, an increased ability of the virus to bind at the Vero cell surface was observed and is likely associated with an increased ability to bind onto cell-surface sialic acid residues. In addition, the kinetics of μ1 disassembly from the virions appears to be altered. The plasmid-based reverse genetics approach confirmed the importance of σ1 amino acids substitutions in VeroAV's ability to efficiently infect Vero cells, although μ1 co-adaptation appears necessary to optimize viral infection. This approach of combining in vitro selection of reoviruses with reverse genetics to identify pertinent amino acids substitutions appears promising in the context of eventual reovirus modification to increase its potential as an oncolytic virus.

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Mechanisms of Apoptosis During Reovirus Infection

Cited by 34 publications

References 50 publications

Activation of Innate Immune Responses in the Central Nervous System during Reovirus Myelitis

Activation of Innate Immune Responses in the Central Nervous System during Reovirus Myelitis

Cloning and characterization of Bax1 and Bax2 genes of Ctenopharyngodon idellus and evaluation of transcript expression in response to grass carp reovirus infection

Amino acids substitutions in σ1 and μ1 outer capsid proteins of a Vero cell-adapted mammalian orthoreovirus are required for optimal virus binding and disassembly

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