Dataset Information

Rules and exceptions: sialic acid variants and their role in determining viral tropism.

ABSTRACT: Sialic acids decorate the surfaces of most mammalian cells and are used by many viruses as attachment receptors. In contrast to other mammals, humans cannot synthesize a version of sialic acid known as N-glycolyl neuraminic acid. This difference is exploited by some viruses to establish tropism. Here we compare recently determined structures of closely related animal and human polyomaviruses and examine their strategies for engaging specific sialic acid variants.

SUBMITTER: Stehle T

PROVIDER: S-EPMC4097780 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rules and exceptions: sialic acid variants and their role in determining viral tropism.

Stehle Thilo T Khan Zaigham M ZM

Journal of virology 20140507 14

Sialic acids decorate the surfaces of most mammalian cells and are used by many viruses as attachment receptors. In contrast to other mammals, humans cannot synthesize a version of sialic acid known as N-glycolyl neuraminic acid. This difference is exploited by some viruses to establish tropism. Here we compare recently determined structures of closely related animal and human polyomaviruses and examine their strategies for engaging specific sialic acid variants. ...[more]

PMID: 24807712

Similar Datasets

Project description:Avian or human influenza A viruses bind preferentially to avian- or human-type sialic acid receptors, respectively, indicating that receptor tropism is an important factor for determining the viral host range. However, there are currently no reliable methods for analyzing receptor tropism biologically under physiological conditions. In this study, we established a novel system using MDCK cells with avian- or human-type sialic acid receptors and with both sialic acid receptors knocked out (KO). When we examined the replication of human and avian influenza viruses in these KO cells, we observed unique viral receptor tropism that could not be detected using a conventional solid-phase sialylglycan binding assay, which directly assesses physical binding between the virus and sialic acids. Furthermore, we serially passaged an engineered avian-derived H4N5 influenza virus, whose PB2 gene was deleted, in avian-type receptor KO cells stably expressing PB2 to select a mutant with enhanced replication in KO cells; however, its binding to human-type sialylglycan was undetectable using the solid-phase binding assay. These data indicate that a panel of sialic acid receptor KO cells could be a useful tool for determining the biological receptor tropism of influenza A viruses. Moreover, the PB2KO virus experimental system could help to safely and efficiently identify the mutations required for avian influenza viruses to adapt to human cells that could trigger a new influenza pandemic. IMPORTANCE The acquisition of mutations that allow avian influenza A virus hemagglutinins to recognize human-type receptors is mandatory for the transmission of avian viruses to humans, which could lead to a pandemic. In this study, we established a novel system using a set of genetically engineered MDCK cells with knocked out sialic acid receptors to biologically evaluate the receptor tropism for influenza A viruses. Using this system, we observed unique receptor tropism in several virus strains that was undetectable using conventional solid-phase binding assays that measure physical binding between the virus and artificially synthesized sialylglycans. This study contributes to elucidation of the relationship between the physical binding of virus and receptor and viral infectivity. Furthermore, the system using sialic acid knockout cells could provide a useful tool to explore the sialic acid-independent entry mechanism. In addition, our system could be safely used to identify mutations that could acquire human-type receptor tropism.

Dataset Information

Rules and exceptions: sialic acid variants and their role in determining viral tropism.

Publications

Rules and exceptions: sialic acid variants and their role in determining viral tropism.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets