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PubMed2026

Genetic Variation and Evolutionary Characteristics of Coxsackievirus B1: F3 Subtype Associated With Hand, Foot and Mouth Disease in China.

Coxsackievirus B1 (CV-B1) is primarily associated with meningitis but can also cause localized outbreaks of hand, foot, and mouth disease (HFMD). This study analyzed the genetic diversity of the VP1 gene in 39 strains of the CVB1 virus isolated from HFMD children across 15 provinces in China between 2010 and 2024, as well as 179 strains from 17 countries. Based on the average nucleotide difference of VP1 gene, we classified CVB1 virus into six genotypes A to F, Notably, genotype F is newly classified. Since 2010, genotype F guadually replaced genotype E as the dominant genotype in China and has further subdivided into three subtypes: F1, F2, and F3, with F3 being the most prevalent subtype in China currently. We specifically study the mild and severe cases within the F3 subtype. Temperature-sensitivity experiments revealed no differences between mild and severe cases of the F3 subtype, and they all belong to temperature-sensitive strains. Interestingly, we found that mild cases of the F3 subtype did not involve recombination, whereas all severe cases of the F3 subtype showed recombination with Coxsackievirus B4 (CVB4). CVB4 has consistently been the primary pathogen responsible for severe neonatal illnesses, suggesting that recombination between the F3 subtype and CVB4 may be associated with the development of severe HFMD. These findings provide fundamental scientific data for further investigation into the epidemiology and genetic characteristics of variants of Coxsackievirus B1 in China.

Humans↗
PubMed1979

Selective polymyositis inducted by coxsackievirus B1 in mice.

A high-passage laboratory strain of coxsackievirus B1 produced a unique myositis that predominantly and profoundly affected hip extensors and, to a lesser extent, hindquarter knee flexors when inoculated into a strain of random-bred newborn mice of Swiss origin (COH mice). The effect was not observed in BALB/c or C3H mice similarly inoculated. In addition to the differences in susceptibility of the mouse strains, it was found that six different low-passage "field" isolates of coxsackie-virus B1 isolated from infected patients varied considerably in their capability to induce these lesions. Thus, selective myositis which is muscle group-specific can be induced in a mouse model with coxsackievirus B1, and both genetic factors of the host and characteristics of the virus strain play a significant role in the pathogenesis of the myositis.

Animals↗
PubMed1976

Pathological changes in the pancreas of mice following infection with Coxsackie B viruses.

Infection of pregnant or non-pregnant mice with Coxsackieviruses B1, B3, B4 or B5 produced a severe pancreatitis consisting of a degeneration of the acinar cells, loss of zymogen granules, infiltration of mononuclear and plasma cells and a replacement of the exocrine tissue with fatty tissue. Coxsackieviruses B2 and B6 did not cause these changes in the period up to 6 weeks following virus injection. Suckling mice did not appear to be more susceptible to pancreatic damage due to these two viruses. Sequential studies on the development of Coxsackievirus B-induced pancreatic lesions indicated that although the changes due to B1, B3, B4 or B5 were similar in type, B3 and B4 exhibited a more rapid action in the tissue and more severe lesions than either B1 or B5. In this work, none of the Coxsackie B viruses examined elicited pathological changes in the islets of Langerhans detectable with the light microscope.

Animals↗
PubMed2026

Molecular Epidemiology of Non-Polio Enterovirus: Insights From L20B Cell Line Adaptation From Children With Acute Flaccid Paralysis in Pakistan.

BACKGROUND: Non-polio enteroviruses (NPEVs) are increasingly implicated in acute flaccid paralysis (AFP), often resembling poliomyelitis and complicating eradication efforts. In Pakistan, limited molecular surveillance has hindered comprehensive characterization. The L20B cell line, designed for poliovirus detection, occasionally supports NPEV replication, challenging AFP case interpretation. METHODS: Between January 2021 and December 2022, 4615 stool samples from AFP cases in children ≤15 years were analyzed. Of these, 435 were identified as NPEVs via L20B cytopathic effects and intertypic differentiation reverse transcription-polymerase chain reaction. VP1 sequencing was performed on 218 representative isolates, yielding 153 high-quality sequences (70.2%). The 224/222 primer set showed superior amplification. Phylogenetic analysis used MUSCLE alignment and the Neighbor-Joining method in MEGA X, with statistical evaluation of epidemiological data. RESULTS: NPEVs were frequently found in L20B-positive AFP cases, highlighting the cell line's limited specificity. Most cases involved children under 5, with a slight male bias. Enterovirus B was predominant (98.0%), especially Echovirus 7 (20.3%) and Echovirus 11 (10.5%), followed by Coxsackievirus B1 and Echovirus 33 (5.9% each). Geographic clustering was noted in Punjab (45.1%), Khyber Pakhtunkhwa (30.7%) and Sindh (20.3%), with seasonal peaks in late summer and early autumn. Phylogenetic data revealed localized Enterovirus B circulation with minimal genetic variation. CONCLUSIONS: The detection of diverse NPEVs in L20B-positive AFP cases emphasizes their relevance in post-polio surveillance. Incorporating routine VP1 sequencing, optimized primer use, and targeted seasonal and regional monitoring is vital to reduce diagnostic uncertainty and inform public health strategies.

Humans↗
PubMed1978

Conjugation of coxsackievirus type B1-B6 immunoglobulins with fluorescein isothiocyanate by a "reversed" dialysis method.

Immunoglobulins from antisera to coxsackievirus B types 1--6 were labeled with fluorescein isothiocyanate by a "reverse" dialysis method of conjugation. Conjugates thus obtained were labeled at reproducible ratios of fluorescein to protein with weight-weight ratios ranging from 5.0 to 7.1 and estimated molar ratios ranging from 2.1 to 2.9. Conjugates were tested on cover-slip HeLa cell cultures by the direct method of staining. Two types of specific immunofluorescence were observed: intensely fluorescent perinuclear masses and discrete foci of bright fluorescence scattered throughout the cytoplasm. Titers of homotypic conjugates varied from 1:40 to 1:160. Heterotypic staining, consisting of a diffused hazy fluorescence, was observed only at the highest concentrations of conjugate and not above the 1:10 dilution. This technique proved to be specific and sensitive for the detection of group B coxsackievirus antigens in HeLa cells but failed in specific detection of the same antigens in samples of the myocardium obtained by biopsy of three patients clinically ill with idiopathic myocarditis.

Antibodies, Viral↗
PubMed1975

Mersalyl: a diuretic with antiviral properties.

Mersalyl (Salyrgan), an organic mercurial diuretic, was tested against human and animal viruses with in vivo model infections in mice and tissue culture systems. Mersalyl was active against coxsackieviruses A21 and B1 in mice if administered intraperitoneally immediately after infection. No effect was observed if intraperitoneal treatment was delayed 1 or 2 h postinfection, or if treatment was administered either subcutaneously or per os. Topical treatment with a 5% aqueous solution of mersalyl produced a statistically significant effect against herpes simplex dermatitis in mice but the substance was inactive against systemic infections in mice with herpes simplex as well as Columbia SK, influenza, Semliki Forest, and Sendai viruses. Contact inactivation of coxsackieviruses A21 and B1 and herpes simplex virus was observed, but mersalyl was inactive in tissue culture against coxackieviruses A21 and B1, herpes simplex, influenza, rhinovirus, Semliki Forest, Sendai, and vaccinia viruses.

Animals↗
PubMed1979

Lesions induced by encephalomyocarditis virus and coxsackievirus B in newborn mice.

Electron microscopic studies of various tissues from virus-infected newborn mice disclosed a consistent form of viral cytonecrotic ultrastructural lesion in divergent types of cells (myocardial, valvular fibroblastic, aortic, exocrine and endocrine pancreatic, and hepatic cells) due to three different picornaviruses (coxsackieviruses B4 and B1 and encephalomyocarditis virus). The lesion is characterized by numerous membrane-vesicle complexes, margination of nuclear chromatin or nuclear pyknosis, dilation of rough endoplasmic reticulum, inflammation, and, at times, mitochondrial swelling. It seems apparent that the finding of this ultrastructural type of cytonecrosis is characteristic of a picornaviral infection regardless of the tissue involved and the offending member of the picornavirus group.

Animals↗
PubMed1978

Course of coxsackie B antibodies during juvenile diabetes.

Sera of 83 patients with insulin-dependent diabetes of early onset were tested for latex agglutination-inhibiting antibodies to coxsackie virus types B1-B5. We could not find any evidence of a causal association between Coxsackie B virus infection and diabetes.

Adolescent↗
PubMed1978

[Pancreatic lesion in newborn mice caused by Coxsackie B1 virus].

Changes in the pancreatic gland manifested by necrosis of excretory cells and marked atrophy of insulae with the loss of beta-cells producing insulin were observed experimentally in suckling mice infected with Coxsackie B1 virus. It is suggested that the above changes of the pancreas may be a model of human diseases caused by Coxsackie viruses, including a model of development of some cases of diabetes.

Animals↗
PubMed1977

[Antibodies in gamma-globulin preparations (author's transl)].

A commerical preparation of gamma-globulin with 16% protein content for i. m. administration, as well as two commercial preparations of 5% protein content for i.v. administration, were tested for their antibodies to different viruses. The highest antibody titres were found in the 16% gamma-globulin. Sufficient levels of antibodies to justify prophylactic use were demonstrated in the case of rubella, measles, polio and EBV, whilst antibodies to mumps, coxsackie A9, B1-5 and herpes simplex type I and II were present to a moderate degree. Only low concentrations of antibodies or none at all were found with respect to influence A and B, para-influenza 1--3, vaccinia, adeno 3 and 7, and echo 4, 6, 9, 18 and HBs-antigen. This study shows that normal gamma-globulin can be used prohylactically against many different viral diseases.

Antibodies, Viral↗
PubMed1979

Type 1 diabetes and Coxsackie virus infection.

The role played by viruses in the aetiopathogenesis of type 1 diabetes mellitus has been studied by several authors; in particular the importance of Coxsackie virus B4 infection has been stated by some authors and not confirmed by others. 43 diabetic children were studied at the time of the diagnosis of the disease. No viruses could be isolated from stools; the titres of anti-Coxsackie viruses B1 to 6 complement fixing antibodies and anti-Coxsackie virus B4 neutralizing antibodies, compared to controls, indicated that Coxsackie virus infection was not associated with the onset of diabetes in these children. A cross-reaction with anti-Coxsackie viruses sera and a human pancreas demonstrated that there are not antigens in common between these viruses and the human pancreas.

Adolescent↗
PubMed1979

The spread of Coxsackie B1 infection.

During June and July 1977 5 junior boys in a boarding school for 800 pupils became ill with a mild infection caused by Coxsackie B1. The school had been taking part in a vaccine trial, and paired blood samples had been taken from new entrants in October 1976 and October 1977. 18% of the boys susceptible to the infection developed antibodies. The results suggest that dormitories are more important than the day-to-day contacts in the spread of infection. The advisability of nursing children with known or suspected enterovirus infections in open wards in hospital is questioned.

Adolescent↗
PubMed1977

Aetiology of juvenile-onset diabetes. A prospective study.

110 people in whom insulin-dependent diabetes developed when they were less than 30 years old were studied as soon as possible after diagnosis. There was evidence for clustering of cases with BW15-positive phenotypes during the winter peak (1976) but not during the autumn peak (1975). Subjects who were BW15-positive, and in particular those who were both B8 and BW15-positive, had higher neutralising antibody titres to Coxsackle virus types B1-B4 58% of cases had islet-cell antibodies (I.C.A.), but the presence of I.C.A. was not correlated with HLA phenotypes or viral antibody titres. In 41 subjects (37%), who gave a definite history of antecedent illness, evidence indicated that this was a precipitating infection and not the initiating event producing islet-cell damage. Nearly half the subjects had had diabetic symptoms for more than 4 weeks before diagnosis.

Adolescent↗
PubMed1975

Ultrastructural myocardial changes produced by viruses.

Some of the ultrastructural pathological alterations in the myocardium produced by viral infections with members of the picornavirus group are described. These alterations varied from mild to severe, with necrosis. In animals infected with Coxsackie B1 virus and EMC virus, readily identifiable viral crystals were frequently found in association with the myocardial lesions by means of electron microscopy. The electron microscope made it possible to study vary early myocardial changes which were not detected with the light microscope. Although the ultrastructural myocardial changes in rheumatic fever have received little attention, the light and electron microscopic findings in the myocardium and valves of the viral-infected animals described here closely resemble those described in man in association with so-called rheumatic heart disease. The type of investigations presented forms a good model for the study of the natural history of ultrastructural pathology produced in all parts of the heart by viruses.

Adolescent↗