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Rhinoviruses, enteroviruses and EV-D68 05/24/25

Colds causing rhinitis, sinusitis, bronchitis, asthma and pneumonia are now prevalent. These rhinoviruses (HRVs) (e.g. Rhinovirus A/B/C) and the enteroviruses (EVs) (e.g. Poliovirus, Coxsackievirus, Echovirus, EV-D68) that will be prevalent in the coming summer and autumn are thought to have a common evolutionary ancestor and are thought to share the same ‘Picornavirus family’. (Both are single-stranded (+) RNA viruses, non-enveloped viruses)
Rhinoviruses (HRVs) mainly infect the upper respiratory tract (causing colds) to the lower respiratory tract, while enteroviruses (EVs) infect the gastrointestinal tract (high fever colds that also affect the stomach), nervous system and central nervous system.
HRVs are acid-sensitive and are easily inactivated by stomach acid, whereas enteroviruses tolerate stomach acid and are more likely to cause gastrointestinal symptoms.

Although there is some similarity in their genome structures to each other, molecular phylogenetic analysis (sequence of VP1 region* and 5’UTR region**) shows that rhinoviruses (HRVs) form a distinct clade from enteroviruses (EVs). Rhinovirus (HRV) is largely divided into A clade (76 types) and B clade (25 types), both of which have been identified as clearly diverging from the enterovirus (EV) clade.

Only the sequence of rhinovirus (HRV) 87 was found to be closer to enteroviruses (especially EV-70) rather than to rhinoviruses, and HRV 87 has since been classified in the genus enterovirus D and re-named enterovirus D68 (EV-D68).

(*VP1 is the major capsid protein of the virus and plays an important role in viral classification and antigenicity determination.)
(**5’UTR (5′ untranslated region) is an untranslated region at the beginning of the genomic RNA of an RNA virus. This part of the genome is not a protein, but plays a role in regulating translation initiation, viral RNA stability and replication control, and is crucial for infectivity.)

Enterovirus D68, although in the enterovirus genus, is strongly characterised as a respiratory virus and is similar to rhinoviruses. It causes wheezing and severe breathing problems as well as upper respiratory tract inflammation. Hence, it is more likely to be severe in infants and children with asthma.
It is easily inactivated by stomach acid and is less likely to cause gastrointestinal symptoms despite being an enterovirus.

Of particular importance, EV-D68 can cause polio-like central nervous system symptoms (acute flaccid paralysis) such as sudden tetraplegia and muscle weakness, although this is rare.

Thus, EV-D68 is a virus with ‘intermediate properties’ between HRV and EV: it can grow in cold culture like HRV, infect the lower respiratory tract like HRV, and infect the nervous system like EV.

EV-D68 is a virus of high medical importance, with large outbreaks occurring every few years in 2014, 2016,2018 and 2024.

In summary, although enterovirus EV-D68 and rhinovirus are genetically closely related in terms of symptoms caused, EV-D68 is a different virus species in the ‘enterovirus genus’ and not in the ‘rhinovirus genus’.

Genetic clustering of all 102 human rhinovirus prototype strains: serotype 87 is close to human enterovirus 70: Journal of General Virology

Human Rhinovirus 87 and Enterovirus 68 Represent a Unique Serotype with Rhinovirus and Enterovirus Features: Journal of Clinical Microbiology