Coxsackievirus B3 replication and pathogenesis

Garmaroudi, Farshid S.; Marchant, David; Hendry, Reid G.; Luo, Honglin; Yang, Decheng; Ye, Xin; Shi, Junyan; McManus, Bruce M.

doi:10.2217/fmb.15.5

Cited by 155 publications

(174 citation statements)

References 253 publications

(262 reference statements)

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“…73 The pathogenic processes discussed here are recognized to be downstream of the encounter between host and virus that includes an enteric portal and involvement of the immune system structurally and functionally at early points in the deadly duel of virus and host. 74,75 …”

Section: Mechanismsmentioning

confidence: 99%

“…Multiple cellular signaling pathways are known to be activated upon viral infection and play a critical role in regulating viral infectivity at various steps of viral lifecycle, including viral entry, replication, release, and evasion from host immune responses. 75 Coyne and Bergelson 84 demonstrated that viral entry into epithelial cells through tight junctions is mediated by Fyn and Abl kinases. Studies have also revealed that the activation of the tyrosine protein kinase p56 lck , a member of the Src family kinases, the extracellular signalregulated kinase 1/2 mitogen-activated protein kinase, and protein kinase B signaling as a result of CVB3 infection of immune and myocardial cells is required for efficient viral replication and is associated with host susceptibility to viral myocarditis.…”

Section: Virus-induced Direct Damagementioning

confidence: 99%

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Myocarditis

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Section: Mechanismsmentioning

confidence: 99%

Section: Virus-induced Direct Damagementioning

confidence: 99%

Myocarditis

et al. 2016

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“…injection, CVB3 replicates to high titers in tissues and causes disease similar to that observed in humans (12)(13)(14), and male mice are more likely to develop severe myocarditis than female mice. Experimental evidence suggests that two mechanisms contribute to CVB3-induced myocarditis in these mouse models: direct viral lysis of infected cardiomyocytes and immunemediated damage of cardiac tissue (15). The latter is hypothesized to be responsible for the sex bias in disease.…”

mentioning

confidence: 97%

Sex-Dependent Intestinal Replication of an Enteric Virus

Robinson

Wang

Pfeiffer

2017

J Virol

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Coxsackievirus is an enteric virus that initiates infection in the gastrointestinal tract before disseminating to peripheral tissues to cause disease, but intestinal factors that influence viral replication are understudied. Furthermore, a sex bias for severe sequelae from coxsackievirus infections has been observed in humans. While mouse models mimicking human pathogenesis have been well characterized, many of these experiments use intraperitoneal injection of coxsackievirus to infect mice, bypassing the intestine. In light of recent studies identifying intestinal factors, such as the microbiota, that alter enteric viral replication, we sought to investigate coxsackievirus replication within the intestine. Here, we orally infected mice with coxsackievirus B3 (CVB3) and found that CVB3 replication in the intestine is sex dependent. CVB3 replicated efficiently in the intestine of male mice but not female mice. Additionally, we found that the type I interferon response and sex hormones can alter both viral replication and lethality. Overall, these data suggest that sex and the immune response play a vital role in CVB3 replication in the intestine and should be considered in light of the sex bias observed in human disease.IMPORTANCE Sex bias in severe sequelae from enteric viral infections has been observed. Since viruses have evolved to achieve optimal levels of fitness in their environmental niches, it is imperative to study viruses at the site of initial replication. Here, we used an oral inoculation system for CVB3, which follows the natural route of infection in the gastrointestinal tract. We found that sex can influence the replication of CVB3 in the intestine. Additionally, the type I interferon response and sex hormones alter both CVB3 intestinal replication and lethality. Overall this work highlights the fact that sex should be considered in investigations of enteric viral replication and pathogenesis.KEYWORDS coxsackievirus B3, intestine, pathogenesis, sex hormones S ex contributes to the frequency and severity of many human diseases (1-3). Epidemiological studies show that men are more susceptible to bacterial, viral, and fungal infections (2). Women, while more resistant to pathogens, are at an increased risk for autoimmune disorders. Sexual dimorphism in disease has been attributed to differential gene expression, sex hormones, and variations in immune function (4). However, sex as a variable in disease models is understudied, limiting our understanding of the mechanism of sex bias in various diseases.Coxsackievirus is a nonenveloped RNA virus from the Picornaviridae family and is implicated in a range of diseases (5-8). In humans, males are twice as likely as females to develop sequelae from coxsackievirus infection (9). While most coxsackievirus infections are self-limiting, they can cause severe disease. In particular, coxsackievirus B3 (CVB3) is a leading cause of viral myocarditis, and extensive cardiac damage can lead to cardiac failure (10, 11). Because there are no current vaccines or ...

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“…The life cycle of enterovirus begins with recognition and binding to receptors on plasma membrane, followed by receptor-mediated endocytosis which results in virus uncoating and release of viral genome RNA (vRNA) into cytoplasm induced by pH change in endosomal compartment [68,69]. Subsequently, vRNA serves as a primary template to translate into a large polyprotein that are cleaved by viral proteases 2A pro , 3C pro and 3CD pro into ten proteins, including four capsid proteins (VP1, VP2, VP3 and VP4), two viral proteases (2A, and 3C), a RNA-dependent-RNA-polymerase (3D), two proteins involved in RNA synthesis (2B, and 2C), and a primer of initiation of RNA synthesis (3AB) [68,69].…”

Section: Enterovirus: Pathogenesis and Life Cyclementioning

confidence: 99%

The interplay of autophagy and enterovirus

Huang

Yue

2020

Seminars in Cell & Developmental Biology

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A B S T R A C T Autophagy, an evolutional conserved lysosomal degradation process, has been implicated to play an important role in cellular defense against a variety of microbial infection. Interestingly, numerous studies found that some pathogens, especially positive-single-strand RNA viruses, actually hijacked autophagy machinery to promote virus infection within host cells, facilitating different stages of viral life cycle, from replication, assembly to egress. Enterovirus, a genus of positive-strand RNA virus, can cause various human diseases and is one of main public health threat globally, yet no effective clinical intervention is available for enterovirus infection. Here we summarized recent literature on how enteroviruses regulate and utilize autophagy process to facilitate their propagation in the host cells. The studies on the interplay between enterovirus and autophagy not only shed light on the molecular mechanisms underlying how enterovirus hijacks cellular components and pathway for its own benefits, but also provide therapeutic option against enterovirus infection.

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Coxsackievirus B3 replication and pathogenesis

Cited by 155 publications

References 253 publications

Myocarditis

Myocarditis

Sex-Dependent Intestinal Replication of an Enteric Virus

The interplay of autophagy and enterovirus

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