A1 Refereed original research article in a scientific journal
Human Parechovirus 1 Infection Occurs via alpha V beta 1 Integrin
Authors: Merilahti P, Tauriainen S, Susi P
Publisher: PUBLIC LIBRARY SCIENCE
Publication year: 2016
Journal: PLoS ONE
Journal name in source: PLOS ONE
Journal acronym: PLOS ONE
Article number: ARTN e0154769
Volume: 11
Issue: 4
Number of pages: 17
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0154769
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 alpha V beta 1, alpha V beta 3 and alpha V beta 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 alpha V beta 1, alpha V beta 3, alpha V beta 6 and alpha 5 beta 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 alpha V beta 1 integrin but not alpha V beta 3 or alpha V beta 6 integrins. To further study the role of beta 1 integrin, we used a mouse cell line, GE11-KO, which is deficient in beta 1 expression, and its derivate GE11-beta 1 in which human integrin beta 1 subunit is overexpressed. HPeV-1 (Harris strain) and three clinical HPeV-1 isolates did not internalize into GE11-KO whereas GE11-beta 1 supported the internalization process. An integrin beta 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 beta 1 integrin on the cell surface, and HPeV-1 and beta 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 alpha V beta 1 integrin without visible receptor clustering.
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 alpha V beta 1, alpha V beta 3 and alpha V beta 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 alpha V beta 1, alpha V beta 3, alpha V beta 6 and alpha 5 beta 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 alpha V beta 1 integrin but not alpha V beta 3 or alpha V beta 6 integrins. To further study the role of beta 1 integrin, we used a mouse cell line, GE11-KO, which is deficient in beta 1 expression, and its derivate GE11-beta 1 in which human integrin beta 1 subunit is overexpressed. HPeV-1 (Harris strain) and three clinical HPeV-1 isolates did not internalize into GE11-KO whereas GE11-beta 1 supported the internalization process. An integrin beta 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 beta 1 integrin on the cell surface, and HPeV-1 and beta 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 alpha V beta 1 integrin without visible receptor clustering.
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