-Associated Polyomavirus Uses a Displaced Binding Site on VP1 to Engage Sialylated Glycolipids


Viruses engage receptors on their host cell to initiate entry and infection. Members within a virus family are known to target different tissues and hosts and exploit different pathogenic mechanisms due to critical changes in receptor specificity. The human Trichodysplasia spinulosa-associated Polyomavirus (TSPyV) is known to cause a rare skin disease in immunocompromised individuals. The pathogenic mechanism includes hyperproliferation of inner root sheath cells, but molecular determinants underlying the infection and the associated disease remain unknown. Here we applied a structural and functional approach to investigate the recognition events during early infection steps of the virus. We found that TSPyV engages sialic acid receptors but employs a novel binding site on the capsid that is shifted in comparison to other structurally characterized polyomaviruses. Cell-based studies demonstrate the relevance of the observed interaction for attachment and infection and suggest that glycolipids, rather than N- and O-linked glycoproteins, are important for infection. Our findings demonstrate exemplarily that receptor recognition by (polyoma-) viruses is highly variable not only in interactions with sialic acids, but also in the location of the binding site on the capsid, providing insights about structural determinants of receptor and host specificity and evolution of these viruses.


Vyšlo v časopise: -Associated Polyomavirus Uses a Displaced Binding Site on VP1 to Engage Sialylated Glycolipids. PLoS Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005112
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1005112

Souhrn

Viruses engage receptors on their host cell to initiate entry and infection. Members within a virus family are known to target different tissues and hosts and exploit different pathogenic mechanisms due to critical changes in receptor specificity. The human Trichodysplasia spinulosa-associated Polyomavirus (TSPyV) is known to cause a rare skin disease in immunocompromised individuals. The pathogenic mechanism includes hyperproliferation of inner root sheath cells, but molecular determinants underlying the infection and the associated disease remain unknown. Here we applied a structural and functional approach to investigate the recognition events during early infection steps of the virus. We found that TSPyV engages sialic acid receptors but employs a novel binding site on the capsid that is shifted in comparison to other structurally characterized polyomaviruses. Cell-based studies demonstrate the relevance of the observed interaction for attachment and infection and suggest that glycolipids, rather than N- and O-linked glycoproteins, are important for infection. Our findings demonstrate exemplarily that receptor recognition by (polyoma-) viruses is highly variable not only in interactions with sialic acids, but also in the location of the binding site on the capsid, providing insights about structural determinants of receptor and host specificity and evolution of these viruses.


Zdroje

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