Parechovirus: neglected for too long?

Abstract

Parechoviruses are non-enveloped, positive-sense, single-stranded RNA viruses that have been isolated from multiple vertebrate species. Infection with these etiologic agents of typically mild childhood respiratory and gastrointestinal illness in humans is nearly universal, and a subset of infected neonates and infants develop severe neurologic diseases. Rodent parechoviruses cause myocarditis, encephalitis, and perinatal death in multiple rodent species. The key steps of the viral life cycle, clinical characteristics, and global burden of these viruses are not well characterized yet, particularly for nonhuman parechoviruses. Here, we review the history of human and nonhuman parechovirus isolation, global seroprevalence and distribution, viral biology, and evolution, considering these factors might contribute to host specificity, virulence, tissue tropism, pathogenesis, host immunity, and population dynamics.

Keywords: parechovirus; picornavirus.

Fig 1

Host range of parechoviruses and directions of transmission. Parechovirus A genotypes were isolated from human specimens. Parechovirus B/Ljungan virus and Parechovirus C strains were isolated from rodents. Parechovirus D strains were isolated from ferrets and bats. Parechovirus E and Parechovirus F were isolated from falcons and geckos, respectively. Confirmed transmission directions are depicted with solid arrows, and potential transmission directions are represented with dashed arrows. Parechovirus-related picornaviruses that share nucleotide sequence and RNA secondary structure similarity with parechoviruses were isolated from asymptomatic ovines and bovines.

Fig 2

Geographic location of initial parechovirus isolation. The map depicts the locations where Parechovirus-A (PeV-A) (red) and Parechovirus-B (PeV-B) (blue) genotypes were initially isolated. PeV-A genotypes were initially isolated from the United States (PeV-A1, PeV-A2, PeV-A5); Japan (PeV-A3 and PeV-A6); The Netherlands (PeV-A4 and PeVA14); Pakistan (PeV-A7); Brazil (PeV-A8); Bolivia (PeV-A9, PeV-A10, PeV-A11, PeV-A12, PeV-A13, PeV-A15, PeV-A16); Ivory Coast (PeV-A17); Ghana (PeV-A18); and Malawi (PeVA19). PeV-B/LV genotypes were isolated from Sweden (LV-1 and LV-2) and the United States (LV-3 and LV-4).

Fig 3

Parechovirus genome organization. (A) Viruses in the Parechovirus A species have cis-acting RNA elements (cre) in the structural protein-encoding region of the genome, contain only one 2A protein with an H-box/NC motif, and certain strains contain an arginine-glycine-aspartic acid (RGD) motif in the VP1 C-terminus. (B) Members of the Parechovirus B-F species have two separate 2A proteins: (i) a prototypical picornavirus 2A protein with an asparagine-proline-glycine-proline (NPG↓P) ribosome skip site sequence, and (ii) 2A2 protein containing H-box/NC motif. Parechovirus B genotypes presumably contain cre elements in the 3B region of the genome. Cre elements for other parechovirus species remain uncharacterized. Current evidence suggests that all parechoviruses contain a type II IRES.