Human parechovirus 3 is a genotype of human parechoviruses within the genus Parechovirus in the family Picornaviridae. Like other parechoviruses it is non‑enveloped and contains a single‑stranded positive‑sense RNA genome of about 7.3 kilobases enclosed in an icosahedral capsid. HPeV‑3 primarily causes sepsis‑like disease in neonates. Transmission occurs through respiratory droplets and the fecal‑oral route, and maternal antibodies do not always protect newborns.
Virology and clinical significance
Human parechovirus 3 replicates in the cytoplasm of host cells by directly translating its RNA genome into a polyprotein that is cleaved into functional viral proteins. The virus appears to have a tropism for endothelial and neuronal tissues, which may explain its propensity to cause systemic and neurologic disease. Infected infants typically present within the first few weeks of life with high fever, irritability, rash and poor feeding; clinicians sometimes describe the phenotype as a “hot, red, angry baby.” Central nervous system involvement can lead to meningitis, meningoencephalitis or seizures, and some patients develop hepatitis, coagulopathy or myocarditis. Laboratory findings often show normal or mildly elevated inflammatory markers despite severe clinical presentation, and cerebrospinal fluid may have a normal cell count. Diagnosis requires detection of viral RNA by reverse‑transcription PCR from blood, cerebrospinal fluid, stool or throat swabs. There is no specific antiviral treatment; highlighting the importance of early recognition and follow‑up.
Outbreaks and observations
Outbreaks of human parechovirus 3 infection have been reported in multiple countries. In 2022 a cluster of 23 infants aged 5 days to 3 months in Tennessee was admitted with parechovirus meningoencephalitis; genotype 3 was responsible for the most severe cases and infections peaked during the summer. Outbreaks have occurred in Australia, Japan and the Netherlands, often following a seasonal pattern. Because HPeV‑3 can mimic bacterial sepsis, improved awareness and inclusion of parechovirus PCR in multiplex panels have led to more diagnoses. Infection control measures such as hand washing and keeping sick individuals away from newborns can reduce transmission. Human parechovirus 3 is a significant cause of sepsis‑like illness and central nervous system infection in neonates. Distinct virological properties and limited maternal immunity contribute to its severity. Prompt recognition and supportive care are essential, and ongoing surveillance will clarify its epidemiology and inform prevention strategies. Related Terms: Human Parechovirus 1, Echovirus 11, Enterovirus A71, Enterovirus D68, Human Rhinovirus C.