Multiple Viral Determinants Mediate Myopathogenicity in Coxsackievirus B1-Induced Chronic Inflammatory Myopathy

Tam, Patricia E.; Weber-Sanders, Melissa L.; Messner, Ronald P.

doi:10.1128/jvi.77.21.11849-11854.2003

Cited by 17 publications

(21 citation statements)

References 30 publications

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“…Meta-analysis shows an association between enteroviruses and myocarditis in 23% of cases (7), although this association is more variable in cases of dilated cardiomyopathy, a serious disease that often leads to a failing heart (61). Mouse models of CVB-induced pancreatitis (94,110), myocarditis (45,52,110), myositis (104,105), and rapid-onset type 1 diabetes (31) which facilitate the study of these diseases have been developed.…”

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confidence: 99%

5′-Terminal Deletions Occur in Coxsackievirus B3 during Replication in Murine Hearts and Cardiac Myocyte Cultures and Correlate with Encapsidation of Negative-Strand Viral RNA

Kim

Tracy

Tapprich

et al. 2005

J Virol

142

251

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Adult human enteroviral heart disease is often associated with the detection of enteroviral RNA in cardiac muscle tissue in the absence of infectious virus. Passage of coxsackievirus B3 (CVB3) in adult murine cardiomyocytes produced CVB3 that was noncytolytic in HeLa cells. Detectable but noncytopathic CVB3 was also isolated from hearts of mice inoculated with CVB3. Sequence analysis revealed five classes of CVB3 genomes with 5 termini containing 7, 12, 17, 30, and 49 nucleotide deletions. Structural changes (assayed by chemical modification) in cloned, terminally deleted 5-nontranslated regions were confined to the cloverleaf domain and localized within the region of the deletion, leaving key functional elements of the RNA intact. Transfection of CVB3 cDNA clones with the 5-terminal deletions into HeLa cells generated noncytolytic virus (CVB3/TD) which was neutralized by anti-CVB3 serum. Encapsidated negative-strand viral RNA was detected using CsCl-purified CVB3/TD virions, although no negative-strand virion RNA was detected in similarly treated parental CVB3 virions. The viral protein VPg was detected on CVB3/TD virion RNA molecules which terminate in 5 CG or 5 AG. Detection of viral RNA in mouse hearts from 1 week to over 5 months postinoculation with CVB3/TD demonstrated that CVB3/TD virus strains replicate and persist in vivo. These studies describe a naturally occurring genomic alteration to an enteroviral genome associated with long-term viral persistence.The six serotypes of the group B coxsackieviruses (CVB1-6) are enteroviruses (Picornaviridae, species HEV-B) (53). The CVB genome is a single-stranded RNA molecule, 7,400 nucleotides (nt) in length, that is encapsidated within an icosahedral shell (74). The 11 viral proteins (83) are encoded by a single open reading frame which is flanked on the 5Ј and 3Ј termini by nontranslated regions (NTRs) (20). The CVB induce numerous human illnesses, including inflammatory heart disease, pancreatitis, and aseptic meningitis and may also trigger the onset of type 1 diabetes (5,31,72,81,82). The CVB were recognized as causes of human heart disease shortly after their description early in the 1950s (26, 27) and remain the enteroviruses most commonly associated with human cardiomyopathies on the grounds of isolation and serology (5,6,34,62,88). Meta-analysis shows an association between enteroviruses and myocarditis in 23% of cases (7), although this association is more variable in cases of dilated cardiomyopathy, a serious disease that often leads to a failing heart (61). Mouse models of CVB-induced pancreatitis (94, 110), myocarditis (45,52,110), myositis (104, 105), and rapid-onset type 1 diabetes (31) which facilitate the study of these diseases have been developed.Enterovirus infections are generally considered to be acute events, with symptoms and virus titers peaking within a few days postinoculation (p.i.) and with virus being cleared by the adaptive immune response (17). However, enterovirus infections can persist under conditions of immunodeficiency (48,51,...

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confidence: 99%

5′-Terminal Deletions Occur in Coxsackievirus B3 during Replication in Murine Hearts and Cardiac Myocyte Cultures and Correlate with Encapsidation of Negative-Strand Viral RNA

Kim

Tracy

Tapprich

et al. 2005

J Virol

142

251

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“…However, a sequence divergence of 12-14% was detected in the 5'UTR between the clinical isolates and their corresponding prototype strains. Mutations in the EV 5'UTR which plays an important role in the control of replication and translation [25], have been proposed as major determinants of cardiovirulence [26], neurovirulence [23], and myopathogenicity [27]. Similar to the 5′ UTR, the EV 3′ UTR contains secondary structural elements and has been shown to play a role in both translation and replication [28].…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of three enteroviral strains isolated in Kuwait from young children with serious conditions

Chehadeh

Ali

Maimoona

2017

J Infect Dev Ctries

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Introduction: Human enteroviruses are single stranded RNA viruses associated with many serious diseases such as encephalitis and myocarditis. They consist of up to 100 immunologically and genetically distinct types. Three enteroviral isolates, 2104, 3936 and 3988, were previously isolated from patients with neurological disorders or sepsis-like illness. In this study, the molecular characterization of the isolates was investigated. Methodology: A full genome sequencing was performed by Sanger method, followed by phylogenetic and bootscanning analyses. A detailed analysis of genetic differences between the clinical and prototype isolates were investigated by mapping polymorphisms at nucleotide and amino acid levels, and by comparing RNA secondary structure in the noncoding regions. Results: Based on the phylogenetic analysis of the VP1 gene and complete genome, 2104 was typed as coxsackievirus B1, 3936 as coxsackievirus B5, and 3988 as echovirus 7. Similarity and bootscan plots provided support for intra-and intertypic recombination with crossover points occurring mainly along the nonstructural coding regions of the isolates. A sequence divergence of 12 to 14% was detected in the 5'-noncoding region between the clinical isolates and their corresponding prototype strains. Synonymous and nonsynonymous substitutions could be also mapped to different coding regions of the isolates, including those coding for the Puff, Knob and the hydrophobic pocket of the capsid. Examination of relative frequencies of synonymous and nonsynonymous substitutions in different coding regions of enteroviral isolates showed no evidence for selective pressure. Conclusion: The results provided a better understanding of the genetic variations, evolution and adaptation of enteroviruses in Kuwait.

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“…CVB3 can cause acute demyelinating diseases, such as acute disseminated myelitis and acute transverse myelitis [21,22] . Intriguingly, persistent CVB infections have been associated with myocarditis [23,24] , diabetes [25] , chronic inflammatory myopathy [26] , and, most recently, Sjögren's disease [27] . In comparison, systemic manifestations by CVA24 and EV70 are rarely reported [28] .…”

Section: Discussionmentioning

confidence: 99%

Characterization of Infections of Human Leukocytes by Non-Polio Enteroviruses

Hwang

Jun²,

Seo³

et al. 2011

Intervirology

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To elucidate the detailed susceptibilities of leukocytes to clinically important non-polio enteroviruses (EVs), primary monocytes and various human leukocyte cell lines were infected with coxsackievirus A24 (CVA24), coxsackievirus B3 (CVB3), and enterovirus 70 (EV70). The permissiveness was then assessed by determining virus replication and resultant cytopathic effects. Different EVs varied markedly in their ability to infect leukocyte cell lines. CVB3 replicated effectively in leukocytes of B-cell, T-cell, and monocyte origin, CVA24 in leukocytes of B-cell and monocyte origin, and EV70 in leukocytes of monocyte origin. Primary monocytes, as well as monocyte-derived U-937 cells, were permissive to all three EVs. We observed a positive correlation between cytotoxicity and active virus replication, except in CVB3-infected monocytes. U-937 cells efficiently generated CVB3 progeny virus without severe cellular damage, including cell death. Moreover, infectivity on leukocytes was not absolutely associated with the availability of viral receptors. These findings suggest that the susceptibility of human leukocytes to non-polio EVs may be responsible for virus transport during the viremic phase, particularly to secondary target organs, and that active replication of CVB3 in all human leukocyte lineages leads to greater dissemination, in agreement with the ability of CVB to cause systemic diseases.

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Multiple Viral Determinants Mediate Myopathogenicity in Coxsackievirus B1-Induced Chronic Inflammatory Myopathy

Cited by 17 publications

References 30 publications

5′-Terminal Deletions Occur in Coxsackievirus B3 during Replication in Murine Hearts and Cardiac Myocyte Cultures and Correlate with Encapsidation of Negative-Strand Viral RNA

5′-Terminal Deletions Occur in Coxsackievirus B3 during Replication in Murine Hearts and Cardiac Myocyte Cultures and Correlate with Encapsidation of Negative-Strand Viral RNA

Molecular characterization of three enteroviral strains isolated in Kuwait from young children with serious conditions

Characterization of Infections of Human Leukocytes by Non-Polio Enteroviruses

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