Human parechoviruses—biology and clinical significance

Differential utilization of poly(rC) binding protein 2 in translation directed by picornavirus IRES elements

“…The family Picornaviridae, consisting of the enterovirus, rhinovirus, cardiovirus, aphthovirus, hepatovirus, and the recently defined parechovirus genera (Stanway & Hyypia, 1999), contains members that are the causative agents of a diverse number of human and animal diseases+ All members of this family of viruses have single-stranded, message-sense RNA genomes of 7-8 kb in length encoding a single, large open reading frame preceded by long, highly structured 59 NCRs of ;600-1200 nt in length+ These 59 NCRs participate in important functions of the virus life cycle, including RNA replication and cap-independent translation initiation (reviewed in Wimmer et al+, 1993)+ The minimal cis-acting RNA element of the picornavirus 59 NCR required for the initiation of cap-independent, internal ribosome entry is commonly known as the internal ribosome entry site (IRES; Jang et al+, 1990)+ Based upon sequence and structural similarities shared between the IRES elements of the six different picornavirus genera, two major groups have been classified+ The enteroviruses and rhinoviruses constitute the type I IRES elements, and the cardioviruses and aphthoviruses comprise the type II IRES elements (Wimmer et al+, 1993)+ The IRES element of the only member of the hepatovirus genus, hepatitis A virus (HAV), cannot easily be classified into either of the major classes based on its primary and secondary structure (Brown et al+, 1994)+ Similarly, the parechovirus IRES elements have not been definitively grouped into either class; however, parechovirus and HAV IRES elements are somewhat related to the type II IRES elements (Ghazi et al+, 1998)+ In addition to the primary and secondary structural differences that distinguish the two classes of IRES elements, additional divergence became apparent when in vitro translation assays were utilized to study picornavirus translation+ Although picornaviruses with type II IRES elements are capable of efficient translation in a variety of in vitro translation extracts, type I IRES elements are more fastidious+ For example, type I IRES elements inefficiently and inaccurately translate in rabbit reticulocyte lysate (RRL), whereas type II elements translate quite efficiently in RRL (Shih et al+, 1978(Shih et al+, , 1979)+ However, the translation of type I IRES elements in RRL can be stimulated by the addition of certain cellular cytoplasmic extracts or crude initiation factor preparations (Brown & Ehrenfeld, 1979;Dorner et al+, 1984;Phillips & Emmert, 1986;Svitkin et al+, 1988)+ Thus, the distinct structural characteristics of type I and type II IRES elements manifest as differences in the transacting cellular factors that are required for type I compared to type II IRES-mediated internal ribosome entry+…”

Evolution and conservation in human parechovirus genomes

“…Picornaviruses consist of economically and socially very important human and animal viruses such as polioviruses, other enteroviruses, rhinoviruses, hepatitis A virus, footand-mouth disease virus and parechoviruses. Currently, parechoviruses consist of two species: human parechovirus (HPeV) and Ljungan virus (LV) (Johansson et al, 2002;Joki-Korpela & Hyypiä, 2001;Stanway & Hyypiä, 1999;Stanway et al, 2000). HPeVs are frequent infectious agents and although they usually cause mild gastroenteritis and respiratory disease in young children, more serious cases, such as flaccid paralysis, encephalitis and myocarditis, have also been reported, particularly associated with HPeV3 infection (Baumgarte et al, 2008;Benschop et al, 2006a Benschop et al, , 2008bEhrnst & Eriksson, 1993;Figueroa et al, 1989;Harvala et al, 2008Harvala et al, , 2009Joki-Korpela & Hyypiä, 2001).…”

TLR8 and TLR7 are involved in the host's immune response to human parechovirus 1

“…Human parechovirus 1 afflicts mainly infants and young children, it causes diarrhoea and respiratory illness, but more serious symptoms such as myocarditis and encephalitis have also been reported [11,15].…”

“…HPEV1 has been shown to cause respiratory infections in children [11]; we therefore investigated whether HPEV1 can induce inflammatory cytokines in airway and lung epithelial cells. A549 lung epithelial cells (Fig.…”

“…Human parechovirus 1 (HPEV1), is an ssRNA virus that has been shown to be the cause of a wide variety of illnesses in young adults and children, causing respiratory symptoms, as well as life-threatening disease including encephalitis and flaccid paralysis [11]. Although intrinsic components of this virus can activate the innate immune system, very little is known about the host's sensing mechanisms of HPEV infection.…”