Analysis of Coxsackievirus B5 Infections in the Central Nervous System in Brazil: Insights into Molecular Epidemiology and Genetic Diversity

Abstract

Coxsackievirus B5 (CVB5) is one of the most prevalent enteroviruses types in humans and causes annual epidemics worldwide. In the present study, we explored viral genetic diversity, molecular and epidemiological aspects of CVB5 obtained from cerebrospinal fluid and stool samples of patients with aseptic meningitis or acute flaccid paralysis, information that is still scarce in Brazil. From 2005 to 2018, 57 isolates of CVB5 were identified in the scope of the Brazilian Poliomyelitis Surveillance Program. Phylogenetic analyses of VP1 sequences revealed the circulation of two CVB5 genogroups, with genogroup B circulating until 2017, further replaced by genogroup A. Network analysis based on deduced amino acid sequences showed important substitutions in residues known to play critical roles in viral host tropism, cell entry, and viral antigenicity. Amino acid substitutions were investigated by the Protein Variation Effect Analyzer (PROVEAN) tool, which revealed two deleterious substitutions: T130N and T130A. To the best of our knowledge, this is the first report to use in silico approaches to determine the putative impact of amino acid substitutions on the CVB5 capsid structure. This work provides valuable information on CVB5 diversity associated with central nervous system (CNS) infections, highlighting the importance of evaluating the biological impact of certain amino acids substitutions associated with epidemiological and structural analyses.

Molecular characterization of coxsackievirus B5 from the sputum of pneumonia children patients of Kunming, Southwest China

“…These deleterious mutations may alter the structural stability of the protein (Table 4 ). Although these substitutions were considered deleterious, we can’t exclude the possibility of a milder infection or even a loss in viral fitness [ 15 ]. Aligned Faulkner, KM35 and KM41 with Pymol.…”

“…Four amino acid mutations were substituted at the N-terminus and C-terminus of the five isolates, and four mutations were in loop regions. The loops are located on the surface of the virion and are easily accessible to the host immune system [ 15 ]. Mutations at the N-terminal significantly changed the structure and spatial position of the N-terminal of VP1 protein.…”

“…A comparative analysis of amino acid mutations was performed using BioEdit 7.09 software. The hydropathy changes in residues of VP1 protein between Faulkner and CVB5 isolates were analyzed using online prediction software Protscale ( https://web.expasy.org/protscale/ ), PROVEAN approach was used to evaluate the possible structural and functional changes in the five sputum isolates VP1 protein compared to the Faulkner [ 15 ]. In PROVEAN, a threshold of − 2.5 was used (a score ≤ − 2.5 was considered deleterious, while a score > − 2.5 was considered neutral).…”

“…Enterovirus B is considered to be a common respiratory pathogen in young children and can cause respiratory wheezing disease, including bronchiolitis and exacerbation of asthma [ 1 , 10 , 16 , 17 ]. CVB5 belongs to the species Enterovirus B of the Picornaviridae family [ 5 , 9 , 23 ] and the genomic RNA is about 7.5 kb long in length and encodes a large polyprotein, which consists of the structural proteins (VP1-4) and other nonstructural proteins [ 15 ]. CVB5 uses DAF as a receptor for virus attachment to cells and it depends on CAR for virus entry and virus replication processes.…”

Clinical Research into Central Nervous System Inflammatory Demyelinating Diseases Related to COVID-19 Vaccines

“…Although the S protein shares similar protein sequences with AQP4 and MOG ( Figure 4 ), there are still some critical factors that may affect the protein structure, including hydropathy, global charge, and volume modifications. These factors have the potential to induce variations in the three-dimensional structures during protein folding, thereby altering the binding affinity with antibodies targeting the S protein [ 74 ]. Further clinical studies and experiments are needed to clarify the association and pathogenic mechanisms between COVID-19 vaccines and CNS IDDs.…”