Human Parechovirus: an Increasingly Recognized Cause of Sepsis-Like Illness in Young Infants

Abstract

Human parechovirus (HPeV) is increasingly being recognized as a potentially severe viral infection in neonates and young infants. HPeV belongs to the family Picornaviridae and is currently divided into 19 genotypes. HPeV-1 is the most prevalent genotype and most commonly causes gastrointestinal and respiratory disease. HPeV-3 is clinically the most important genotype due to its association with severe disease in younger infants, which may partly be explained by its distinct virological properties. In young infants, the typical clinical presentation includes fever, severe irritability, and rash, often leading to descriptions of "hot, red, angry babies." Infants with severe central nervous system (CNS) infections are at an increased risk of long-term sequelae. Considering the importance of HPeV as a cause of severe viral infections in young infants, we recommend that molecular diagnostic techniques for early detection be included in the standard practice for the investigation of sepsis-like illnesses and CNS infections in this age group.

Keywords: HPeV; human parechovirus; infants; neonates; pediatrics; picornavirus; sepsis.

FIG 1

Structure of the human parechovirus virion. (Republished from reference with permission of the publisher.)

FIG 2

Genome organization of human parechovirus. (Republished from reference with permission of the publisher.)

FIG 3

Cell entry and innate immune response. HPeV attaches to the cell surface by interaction of the RGD motif with αVβ1 integrin. The clathrin-dependent pathway facilitates the internalization of HPeV into endosomes, where a signaling cascade is mediated. Upon the activation of TLR7 and TLR8, the adaptor protein MyD88 stimulates NF-κB expression. The cooperative binding of the NF-κB p65 subunit, IFN regulatory factor 3 (IRF-3), and activator protein 1 (AP-1) to the type I IFN promoter region of the DNA induces IFN-β gene transcription (20), which results in the induction of the proinflammatory cytokines IFN-β, tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) (49).

FIG 4

Examples of clinical features of severe HPeV infection. (Republished from reference with permission of Oxford University Press.)