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A Naturally Occurring Antiviral Ribonucleotide Encoded By The Human Genome: A Unifying Mechanism for the Antiviral Effects of the Radical SAM Protein Viperin
Başlık:
A Naturally Occurring Antiviral Ribonucleotide Encoded By The Human Genome: A Unifying Mechanism for the Antiviral Effects of the Radical SAM Protein Viperin
Yazar:
Gizzi, Anthony S., author.
ISBN:
9780438060333
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (274 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Steven C. Almo.
Özet:
Viperin, a member of the radical S-adenosyl-L-methionine (SAM) superfamily of enzymes, is an interferon inducible protein implicated in inhibiting the replication of a remarkable range of RNA and DNA viruses. This work demonstrates that viperin catalyzes the conversion of cytidine triphosphate (CTP) to 3'-deoxy-3',4'-didehydro-CTP (ddhCTP), a previously undescribed biologically relevant molecule, via a SAM-dependent radical mechanism. Subsequently, we found that mammalian cells expressing viperin, and macrophages stimulated with IFN-a, produce substantial quantities of ddhCTP.
We next identified the in vivo role of ddhCTP, demonstrating that it acts as a chain terminator for several viral RNA-dependent RNA-polymerases, including Zika, Dengue and West Nile. Further, by applying the nucleoside (ddhC) - a dephosphorylated version of ddhCTP - we found that it is capable of entering mammalian cells where it is metabolized to the active triphosphopshate form, ddhCTP, and consequently restricts the replication of Zika virus.
Notlar:
School code: 0266
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