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An Interaction between Glutathione and the Capsid Is Required for the Morphogenesis of C-Cluster Enteroviruses
Enteroviruses are plus stranded RNA viruses in the Picornaviridae family that cause as many as 3 billion infections per year. Enterovirus morphogenesis, which involves the encapsidation of newly made viral RNAs, has been studied for many years but the process is still poorly understood. Elucidation of this process is important for the development of drug treatments for a variety of human diseases. We describe the role of glutathione, an important cellular reducing agent, in enterovirus morphogenesis by studying the inhibition of GSH biosynthesis with BSO on viral proliferation. We discovered that GSH directly interacts with viral capsid precursors and the mature virus. In the presence of BSO the accumulation of a small capsid precusor (pentamer) is reduced and consequently no mature viruses are produced in virus-infected cells. Drug resistant viruses are easily isolated with mutations located in two of the capsid proteins, VP1 and VP3. We propose a model to explain the role of GSH in enterovirus morphogenesis, which is to stabilize the capsid precursors and the mature virus during and after the encapsidation of the progeny viral RNA by direct interaction with capsid proteins.
Vyšlo v časopise: An Interaction between Glutathione and the Capsid Is Required for the Morphogenesis of C-Cluster Enteroviruses. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004052
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004052Souhrn
Enteroviruses are plus stranded RNA viruses in the Picornaviridae family that cause as many as 3 billion infections per year. Enterovirus morphogenesis, which involves the encapsidation of newly made viral RNAs, has been studied for many years but the process is still poorly understood. Elucidation of this process is important for the development of drug treatments for a variety of human diseases. We describe the role of glutathione, an important cellular reducing agent, in enterovirus morphogenesis by studying the inhibition of GSH biosynthesis with BSO on viral proliferation. We discovered that GSH directly interacts with viral capsid precursors and the mature virus. In the presence of BSO the accumulation of a small capsid precusor (pentamer) is reduced and consequently no mature viruses are produced in virus-infected cells. Drug resistant viruses are easily isolated with mutations located in two of the capsid proteins, VP1 and VP3. We propose a model to explain the role of GSH in enterovirus morphogenesis, which is to stabilize the capsid precursors and the mature virus during and after the encapsidation of the progeny viral RNA by direct interaction with capsid proteins.
Zdroje
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