Human Parechovirus 1 Infection Occurs via ?V?1 Integrin.

ABSTRACT: Human parechovirus 1 (HPeV-1) (family Picornaviridae) is a global cause of pediatric respiratory and CNS infections for which there is no treatment. Although biochemical and in vitro studies have suggested that HPeV-1 binds to ?V?1, ?V?3 and ?V?6 integrin receptor(s), the actual cellular receptors required for infectious entry of HPeV-1 remain unknown. In this paper we analyzed the expression profiles of ?V?1, ?V?3, ?V?6 and ?5?1 in susceptible cell lines (A549, HeLa and SW480) to identify which integrin receptors support HPeV-1 internalization and/or replication cycle. We demonstrate by antibody blocking assay, immunofluorescence microscopy and RT-qPCR that HPeV-1 internalizes and replicates in cell lines that express ?V?1 integrin but not ?V?3 or ?V?6 integrins. To further study the role of ?1 integrin, we used a mouse cell line, GE11-KO, which is deficient in ?1 expression, and its derivate GE11-?1 in which human integrin ?1 subunit is overexpressed. HPeV-1 (Harris strain) and three clinical HPeV-1 isolates did not internalize into GE11-KO whereas GE11-?1 supported the internalization process. An integrin ?1-activating antibody, TS2/16, enhanced HPeV-1 infectivity, but infection occurred in the absence of visible receptor clustering. HPeV-1 also co-localized with ?1 integrin on the cell surface, and HPeV-1 and ?1 integrin co-endocytosed into the cells. In conclusion, our results demonstrate that in some cell lines the cellular entry of HPeV-1 is primarily mediated by the active form of ?V?1 integrin without visible receptor clustering.

SUBMITTER: Merilahti P 

PROVIDER: S-EPMC4851366 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature