Coxsackievirus B4 is a positive-sense, single-stranded RNA virus and one of the six serotypes that comprise the group B coxsackieviruses. Like other picornaviruses, it lacks an envelope and has an icosahedral capsid about 30\u00a0nm in diameter. The virus belongs to the Enterovirus genus and is globally distributed.
Structure and pathogenesis
Coxsackievirus B4 shares structural features with other Enterovirus\u00a0B members. Its genome is roughly 7.3\u00a0kb and encodes a polyprotein that is cleaved into structural and non\u2011structural proteins. The non\u2011enveloped virion is resistant to solvents and low pH, enabling survival in the gastrointestinal tract. Entry occurs through binding of the coxsackievirus\u2013adenovirus receptor on epithelial and cardiac cells; the virus subsequently delivers its RNA into the cytoplasm where translation and replication are initiated via an internal ribosomal entry site. Coxsackievirus\u00a0B4 displays a tropism for natural killer cells and pancreatic \u03b2\u2011islet cells, and infection can induce apoptosis of \u03b2\u00a0cells leading to insulitis and impaired insulin secretion. In animal studies, the genome and proteins assemble in the endoplasmic reticulum, and new virions exit the cell through cytolysis. Because this virus can resist stomach acid and common disinfectants, it spreads readily by the faecal\u2013oral route, contaminated surfaces or respiratory droplets. Although infections are often mild or asymptomatic, neonates are especially vulnerable, and systemic infection can result in myocarditis, meningoencephalitis, hepatitis or pancreatitis. Coxsackievirus\u00a0B4 circulates worldwide and co\u2011circulates with other enteroviruses. Transmission is influenced by seasonality, with peaks in late summer and autumn. There is evidence that persistent infection or autoimmune responses to the virus may contribute to the development of type\u00a01 diabetes. Despite numerous experimental models, no specific antiviral therapy exists; supportive care remains the mainstay of treatment
Clinical features and public health notes
Infections with Coxsackievirus\u00a0B4 can manifest in various ways. Typical features resemble those caused by other enteroviruses: mild fever, sore throat and gastrointestinal upset. However, this serotype has been associated with herpangina, tonsillitis and pharyngitis, and severe outcomes may include myocarditis, meningoencephalitis and hepatitis in newborns. Animal studies show that infection of pregnant mice can result in transplacental transmission and pancreatic abnormalities in offspring, suggesting that vertical transmission may contribute to developmental complications. Reports also indicate that Coxsackievirus\u00a0B4 persists in organs such as the kidneys in mouse models, emphasising its ability to establish chronic infection. The virus is environmentally resilient and can persist on fomites; rigorous handwashing, disinfection and avoidance of contact with infected secretions remain key preventive measures. Coxsackievirus\u00a0B4 is a ubiquitous Enterovirus\u00a0B serotype capable of causing a spectrum of diseases. While many infections are asymptomatic, the virus’s affinity for pancreatic and cardiac tissue underlies its involvement in severe neonatal disease and its proposed link to type\u00a01 diabetes. Improved surveillance and basic hygiene remain essential to limit transmission. Related Terms: Coxsackievirus\u00a0B1, Coxsackievirus\u00a0B3, Coxsackievirus\u00a0B5, Coxsackievirus\u00a0B6, Enterovirus\u00a0B