Picornaviruses that infect humans form one of the largest virus groups with almost three hundred virus types. They include significant enteroviral pathogens such as rhino-, polio-, echo-, and coxsackieviruses and human parechoviruses that cause wide range of disease symptoms. Despite the economic importance of picornaviruses, there are no antivirals. More than ten cellular receptors are known to participate in picornavirus infection, but experimental evidence of their role in cellular infection has been shown for only about twenty picornavirus types. Three enterovirus types and one parechovirus have experimentally been shown to bind and use integrin receptors in cellular infection. These include coxsackievirus A9 (CV-A9), echovirus 9, and human parechovirus 1 that are among the most common and epidemic human picornaviruses and bind to αV-integrins via RGD motif that resides on virus capsid. In contrast, echovirus 1 (E-1) has no RGD and uses integrin α2β1 as cellular receptor. Endocytosis of CV-A9 has recently been shown to occur via a novel Arf6- and dynamin-dependent pathways, while, contrary to collagen binding, E-1 binds inactive β1 integrin and enters via macropinocytosis. In this paper, we review what is known about receptors and endocytosis of integrin-binding human picornaviruses. 1. Introduction Picornaviruses (family Picornaviridae) include a diverse group of viruses, arguably best known not only as causes of devastating acute human (polio) and animal diseases (foot and mouth disease) but also by as the most common infectious disease, common cold, caused by human rhinoviruses, aseptic meningitis caused by coxsackieviruses, and more recently by severe CNS infections of newborns caused by human parechoviruses [1–4]. Clinical manifestations of picornaviruses are variable, including respiratory symptoms, gastroenteritis, rash, myocarditis, neonatal sepsis-like disease, and infections of the central nervous system such as acute flaccid paralysis, meningitis, and encephalitis [5–8]. Some virus types have also been linked to chronic diseases such as type 1 diabetes mellitus [9, 10] and wheezing illnesses that may develop into asthma [11, 12]. In spite of clinical importance of picornaviruses, there are no approved drugs against them, and the only vaccines are against three poliovirus types and hepatitis A virus . Currently, there are twelve genera with 29 species in the family Picornaviridae. Six genera contain virus types that infect humans (Enterovirus, Cardiovirus, Aphthovirus, Parechovirus, Hepatovirus, and Kobuvirus) [13, 14]. The genus
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