Molecular mechanisms of genome expression of coxsackievirus B3 that belongs to enteroviruses

Dutkiewicz, Mariola; Świątkowska, Agata; Ojdowska, Agata; Smólska, Barbara; Dymarek-Babś, Teresa; Jasinska, Anna J.; Ciesiołka, Jerzy

doi:10.5114/bta.2012.46595

Cited by 6 publications

(6 citation statements)

References 41 publications

(66 reference statements)

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“…The molecular details of CVB-associated myocarditis are well-known. Coxsackieviruses enter cardiomyocytes by binding to the co-receptors DAF (decay-accelerating factor) and CAR (coxsackievirus and adenovirus receptor) on the cell membrane [33]. Following internalization, the positive-sense single-stranded RNA genome is translated to produce a single polyprotein.…”

Section: Enterovirusesmentioning

confidence: 99%

“…The polyprotein is then cleaved by viral proteases to generate proteins necessary for replication, capsid formation, and cell lysis. Importantly, the viral proteases also cleave host factors to enhance viral proliferation and inactivate immune responses [33]. For example, CVB proteases cleave host translation initiation factors to promote cap-independent translation to favor viral translation [34,35].…”

Section: Enterovirusesmentioning

confidence: 99%

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Viruses in the Heart: Direct and Indirect Routes to Myocarditis and Heart Failure

Martens

Accornero

2021

Viruses

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Viruses are an underappreciated cause of heart failure. Indeed, several types of viral infections carry cardiovascular risks. Understanding shared and unique mechanisms by which each virus compromises heart function is critical to inform on therapeutic interventions. This review describes how the key viruses known to lead to cardiac dysfunction operate. Both direct host-damaging mechanisms and indirect actions on the immune systems are discussed. As viral myocarditis is a key pathologic driver of heart failure in infected individuals, this review also highlights the role of cytokine storms and inflammation in virus-induced cardiomyopathy.

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Section: Enterovirusesmentioning

confidence: 99%

Section: Enterovirusesmentioning

confidence: 99%

Viruses in the Heart: Direct and Indirect Routes to Myocarditis and Heart Failure

Martens

Accornero

2021

Viruses

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“…It is known, that enteroviruses 3AB precursor protein localizes the viral replication complex to the surface of membranous vesicles and acts as a cofactor to stimulate the activity of 3D polymerase (3Dpol). Genome replication of CVB3 has been described in details [11]. It is catalyzed by the viral RNAdependent RNA polymerase in association with a number of viral and host proteins.…”

Section: Cvb Lifecyclementioning

confidence: 99%

Development of antiviral therapeutics combating coxsackievirus type B3 infection

Volobueva

Zarubaev

Lantseva

2021

Russian Journal of Infection and Immunity

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Enteroviruses are highly diverse group of single-stranded positive RNA viruses belonging to Enterovirus genus from Picornaviridae family. They are the most prevalent viruses in the world. Enteroviruses normally cause seasonal self-limiting infections but they are also known as causative infectious agents of encephalitis, myocarditis, poliomyelitis, acute heart failure and sepsis. Genetic plasticity of enteroviruses allows for widespread epidemics and sporadic outbreaks to occur (for example, outbreaks of Enterovirus D68 and Enterovirus 71). Type B Coxsackieviruses of Enterovirus B species is one of commonly identified infectious agents associated predominantly with mild upper respiratory and gastrointestinal illnesses. Nevertheless, Coxsackieviruses B3 infection can result in severe myocarditis leading ultimately to heart failure. The pathogenesis of Coxsackieviruses B3 induced myocarditis is well studied, and it is mediated by both direct injury mediated by viral proteases and indirect damage secondary to host immune responses. There are no approved direct antiviral medications for the treatment of enteroviral infection in particular Coxsackieviruses B3 myocardial infection to date. Neither are there ongoing clinical trials in the field of Coxsackieviruses B3 infection treatment or prophylaxis. Available treatment strategies are mainly supportive to stabilize the patient condition and to relieve discomforts. Possibly, the relatively small market for anti-enteroviral drugs prevents pharma industry from new drug development. The lifecycle of Coxsackieviruses B3 have been extensively studied and attractive targets for drug design are known. The aim of the present review is to describe the current state of the field of antiviral drug design against Coxsackieviruses B3 infection with special focus on direct-acting antivirals, though host factor-targeting inhibitors (including compounds from medicinal plant extracts) are mentioned too. The following categories of direct Coxsackieviruses B3 inhibitors are discussed in details: capsid binders (pleconaril and its derivatives), viral 3C protease inhibitors (rupintrivir and its analogs), drugs, targeting the viral replication (both nucleoside analogs and non-nucleoside inhibitors). Results of drug repurposing screens for amiloride, benzerazide, dibucaine and fluoxetine are also included.

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“…The internal ribosome entry site (IRES), a S-D-like region in configuration and rich in pyrimidine, exists in the 5′untranslated region and binds to ribosome to start viral replication [11], nt88-181 is the region which is a critical determinant of viral myocardial virulence. There was a pre-determined stem-loop structure (SLII) between nt88 and 181 [12], and substitution of the SLII of CVB3/20 with the SLII from CVB3/CO results in a strain which cannot induce myocarditis; but substitution of CVB3/AS or CVB3/20 in the region can restore myocardial virulence of the strain.…”

Section: Introductionmentioning

confidence: 99%

“…Of note, the 5′untranslated region of CVB3 strains is the main region determining viral virulence, and specific nucleotide variation in the 5′untranslated region may be closely related to different viral virulence, In fact, the mutation of nucleotide U at nucleotide position 234 in the 5′untranslated region of CVB3 strain to C caused its cardiac toxicity significantly reduced. The internal ribosome entry site (IRES), a S-D-like region in configuration and rich in pyrimidine, exists in the 5′untranslated region and binds to ribosome to start viral replication [ 11 ], nt88-181 is the region which is a critical determinant of viral myocardial virulence. There was a pre-determined stem-loop structure (SLII) between nt88 and 181 [ 12 ], and substitution of the SLII of CVB3/20 with the SLII from CVB3/CO results in a strain which cannot induce myocarditis; but substitution of CVB3/AS or CVB3/20 in the region can restore myocardial virulence of the strain.…”

Section: Introductionmentioning

confidence: 99%

The whole genome sequence of Coxsackievirus B3 MKP strain leading to myocarditis and its molecular phylogenetic analysis

Liu

Xiang

et al. 2014

Virol J

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BackgroundIn recent years, the reported infection cases by coxsackievirus (CV) have been on the rise. In order to reveal the relationship between the nucleotide and amino acid sequences and the viral virulence of the CVB3/MKP strain causing myocarditis, we initially confirmed the virulence of the strain in myocardial tissue and then carried out the whole genome sequencing of CVB3/MKP strain and performed a phylogenetic analysis among different CVB3 strains.MethodsCVB3/MKP infected mouse model was established to check lesions of myocardial tissue in mice using immunohistochemical detection at different periods. RT-PCR analysis was used to amplify seven fragments covering the whole viral sequence and comparable analysis was performed.ResultsThe immunohistochemical results showed that particles of CVB3/MKP virus persisted in the cardiac tissue and caused severe pathology. The length of whole genome sequence of CVB3/MKP strain was 7400 bp. CVB3/MKP had 99.7% and 99.6% homology in nucleotide sequence with CVB3/28 and non-virulent CVB3/0, respectively. The former can induce pancreatitis and myocarditis. The nucleotide sequence in the 5′untranslated region of CVB3/MKP strain shared 99.6% and 99.5% homology with CVB3/20 and CVB3/Nancy, respectively.ConclusionWe confirmed in our animal experiments that CVB3/MKP had cardiotoxicity. CVB3/MKP, CVB3/28, and CVB3/0 may share evolutionary convergence and the 5′untranslated region (5′UTR) may be associated with virulence phenotype. Our findings will provide a basis for identifying the genomic determinant of viral virulence of CVB3/MKP strain and phylogenetic relationship among different CVB3 strains.

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Molecular mechanisms of genome expression of coxsackievirus B3 that belongs to enteroviruses

Cited by 6 publications

References 41 publications

Viruses in the Heart: Direct and Indirect Routes to Myocarditis and Heart Failure

Viruses in the Heart: Direct and Indirect Routes to Myocarditis and Heart Failure

Development of antiviral therapeutics combating coxsackievirus type B3 infection

The whole genome sequence of Coxsackievirus B3 MKP strain leading to myocarditis and its molecular phylogenetic analysis

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