Enfermedad mano pie boca en adultos inmunocompetentes. Serie de casos

Resumen La Enfermedad mano pie boca es una patología exantemática viral muy contagiosa, de predominio en la edad pediátrica. Sus agentes etiológicos más frecuentes son los virus Coxsackie y Enterovirus. Se caracteriza clínicamente por la presencia de fiebre, erosiones en mucosa bucal y exantema máculo vesicular en regiones acrales. Generalmente se autolimita, pero puede presentar complicaciones severas con compromiso neurológico, pulmonar y cardíaco. Se han observado brotes mundiales, por lo que actualmente es considerada un problema de salud pública emergente, tanto en poblaciones pediátricas como adultos. Se presentan casos de pacientes adultos inmunocompetentes con transmisión intrafamiliar de Coxsackie B, sin complicaciones severas. Estos casos muestran la importancia de la prevención para evitar brotes epidémicos, además de destacar la presentación infrecuente en adultos inmunocompetentes.

Fatal Enterovirus-related Myocarditis in a Patient with Devic’s Syndrome Treated with Rituximab

Enteroviruses are a frequent source of infection and among the most common central nervous system viral pathogens. Enteroviruses – in particular, the Coxsackie B viruses – are a known cause of myocarditis. Rituximab is a genetically engineered chimeric anti-CD20 monoclonal antibody. Many reports in the literature suggest a higher risk of infection following repeated rituximab therapy, including viral infection. However, observations of enterovirus-related myocarditis in the context of rituximab treatment are scarce. The authors describe the case of a patient with neuromyelitis optica spectrum disorder who developed severe and fatal enterovirus-related myocarditis after rituximab therapy with a difficult differential diagnosis of autoimmune or giant-cell myocarditis. This case highlights the importance of complete diagnostic workup in difficult cases of myocarditis, including endomyocardial biopsies.

Up-to-date approaches to forecast of epidemiological situation with incidence of enteroviral meningitis

This work evaluates the results of long-term dynamic monitoring of non-polio enteroviruses (NPEV) circulation in the indicator subpopulation in Yekaterinburg (children aged 3 to 6 years old), isolation of this group of viruses from specimens of sewage and the spectrum of causative agents detected in the liquor of patients with enteroviral meningitis (EVM). We established a high comparability rate of Coxsackie B and ECHO virus serotypes etiologically significant in EVM and isolated from healthy carriers. NPEV detected in sewage waters over the observation period were presented mainly by Coxsackie B viruses (84.0 %), while ECHO viruses (75.6 %) dominated among the causative agents of EVM. A conclusion was made about low informative value of the sewage study results for evaluation and forecast of the EVM epidemic situation as well as about the rationale for including the screening studies of NPEV circulation in the indicator subpopulation into the system of virological and molecular genetic monitoring.

Genetic Susceptibility of the Host in Virus-Induced Diabetes

Enteroviruses, especially Coxsackie B viruses, are among the candidate environmental factors causative of type 1 diabetes. Host genetic factors have an impact on the development of virus-induced diabetes (VID). Host background, in terms of whether the host is prone to autoimmunity, should also be considered when analyzing the role of target genes in VID. In this review, we describe the genetic susceptibility of the host based on studies in humans and VID animal models. Understanding the host genetic factors should contribute not only to revealing the mechanisms of VID development, but also in taking measures to prevent VID.

Single-Point Mutations within the Coxsackie B Virus Receptor-Binding Site Promote Resistance against Soluble Virus Receptor Traps

ABSTRACT Coxsackie B viruses (CVB) cause a wide spectrum of diseases, ranging from mild respiratory syndromes and hand, foot, and mouth disease to life-threatening conditions, such as pancreatitis, myocarditis, and encephalitis. Previously, we and others found that the soluble virus receptor trap sCAR-Fc strongly attenuates CVB3 infection in mice. In this study, we investigated whether treatment with sCAR-Fc results in development of resistance by CVB3. Two CVB3 strains (CVB3-H3 and CVB3 Nancy) were passaged in HeLa cells in the presence of sCAR-Fc. The CVB3-H3 strain did not develop resistance, whereas two populations of CVB3 Nancy mutants emerged, one with complete (CVB3M) and one with partial (CVB3K) resistance. DNA sequence alignment of the resistant virus variant CVB3M with CVB3 Nancy revealed an amino acid exchange from Asn(N) to Ser(S) at position 139 of the CVB3 capsid protein VP2 (N2139S), an amino acid predicted to be involved in the virus’s interaction with its cognate receptor CAR. Insertion of the N2139S mutation into CVB3-H3 by site-directed mutagenesis promoted resistance of the engineered CVB3-H3N2139S to sCAR-Fc. Interestingly, development of resistance by CVB3-H3N2139S and the exemplarily investigated CVB3M-clone 2 (CVB3M2) against soluble CAR did not compromise the use of cellular CAR for viral infection. Infection of HeLa cells showed that sCAR-Fc resistance, however, negatively affected both virus stability and viral replication compared to that of the parental strains. These data demonstrate that during sCAR-Fc exposure, CVB3 can develop resistance against sCAR-Fc by single-amino-acid exchanges within the virus-receptor binding site, which, however, come at the expense of viral fitness. IMPORTANCE The emergence of resistant viruses is one of the most frequent obstacles preventing successful therapy of viral infections, representing a significant threat to human health. We investigated the emergence of resistant viruses during treatment with sCAR-Fc, a well-studied, highly effective antiviral molecule against CVB infections. Our data show the molecular aspects of resistant CVB3 mutants that arise during repetitive sCAR-Fc usage. However, drug resistance comes at the price of lower viral fitness. These results extend our knowledge of the development of resistance by coxsackieviruses and indicate potential limitations of antiviral therapy using soluble receptor molecules.