Coxsackievirus B6 is the sixth serotype of the group B coxsackieviruses in the Enterovirus B species. This positive-sense RNA virus is non-enveloped with an icosahedral capsid approximately 30 nm in diameter.
Structure and pathogenesis
Coxsackievirus B6 (CVB6) has a linear, positive-sense RNA genome roughly 7.4 kb in length and encodes a single polyprotein that is cleaved into structural (VP1–VP4) and non‑structural proteins. Like other members of the Picornaviridae family, it lacks a lipid envelope, which contributes to its stability in the environment and resistance to solvents and low pH. The virus attaches to host cells using the coxsackievirus–adenovirus receptor and related molecules, and its RNA genome acts directly as mRNA. Translation is initiated via an internal ribosomal entry site at the 5′ untranslated region, after which replication occurs in the cytoplasm. Viral assembly takes place on intracellular membranes, and progeny virions leave the cell by lysis. Transmission of CVB6 is predominantly faecal–oral, and respiratory droplets or contaminated surfaces can also spread the virus. After replication in the oropharynx and gastrointestinal tract, viraemia enables dissemination to target organs. Clinically, CVB6 is less frequently reported than other serotypes, but laboratory and animal studies show that group B coxsackieviruses, including CVB6, can affect the heart, brain, liver and pancreas, causing myocarditis, encephalitis, myelitis, pancreatitis, hand‑foot‑and‑mouth disease and even death in severe cases. Neonatal mouse models infected with CVB6 strains develop weight loss, limb paralysis and high mortality, indicating its neurotropic and cardiotropic potential. Epidemiological data in humans are limited, but CVB6 has been detected sporadically in cases of acute flaccid paralysis and aseptic meningitis. Interestingly, some research suggests that infection with CVB6 or CVB3 might offer immunological cross‑protection against type 1 diabetes, contrasting with the diabetogenic effects associated with CVB4. No vaccine or specific antiviral exists for CVB6; prevention relies on hygiene, sanitising surfaces and avoiding contact with infected secretions.
Research findings and clinical considerations
Infections with CVB6 often go unrecognised because most cases produce nonspecific symptoms such as fever, malaise and gastrointestinal upset. Reports of CVB6 associated with severe disease are rare but informative. Experimental inoculation of neonatal BALB/c mice with CVB6 strains has reproduced severe disease characterised by weight loss, hind‑limb paralysis and death, emphasising neurovirulence in immature hosts. Some case reports have documented CVB6 in patients with acute flaccid paralysis and aseptic meningitis, indicating that the virus can cross the blood‑brain barrier. Given the limited human data, clinicians should consider CVB6 when encountering unexplained viral myocarditis or central nervous system infection during enterovirus season. Because CVB6, like other enteroviruses, is shed in stool for extended periods, thorough handwashing and surface disinfection are essential to limit transmission. Coxsackievirus B6 is a relatively uncommon Enterovirus B serotype, yet it possesses the same structural and pathogenic potential as its better‑known relatives. While most infections are likely subclinical, experimental evidence shows that CVB6 can cause severe disease in neonatal animals and has been implicated sporadically in human neurological illness. Ongoing surveillance and adherence to basic hygiene remain the primary defences against this virus. Related Terms: Coxsackievirus B5, Coxsackievirus B4, Coxsackievirus B3, Enterovirus B, Coxsackievirus B1