The location of the polio genome protein in viral RNAs and its implication for RNA synthesis

Nomoto, Akio; Detjen, B M; Pozzatti, Rudy; Wimmer, Eckard

doi:10.1038/268208a0

Cited by 265 publications

(209 citation statements)

References 19 publications

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“…Biochemical studies have shown that VPg is linked not only to virion RNA, but also to negative strand (genome complement) RNA (4) and to nascent strands of the replicative intermediate (3,4). On the basis of these findings, we (2,4) and others (3) have suggested that VPg may be involved in genome replication, possibly in the initiation of RNA synthesis (4).…”

mentioning

confidence: 99%

“…Polio VPg is hydrophobic (1,2) and basic (net charge of +7 at pH 7.5, ref. 4) and has a molecular weight of 4000-6000 as determined by polyacrylamide gel electrophoresis (2,5,7).…”

mentioning

confidence: 99%

“…The protein is virus-coded (2, 7) and linked to the 5'-terminal uridylate of the RNA (4,7,8). Polio VPg is hydrophobic (1,2) and basic (net charge of +7 at pH 7.5, ref.…”

mentioning

confidence: 99%

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O4-(5'-uridylyl)tyrosine is the bond between the genome-linked protein and the RNA of poliovirus.

Rothberg¹,

Harris²,

Nomoto³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

227

134

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Virion RNA of poliovirus type 1 has been analyzed for the linkage between genome-protein VPg and the polyribonucleotide chain. Hydrolysis of the linkage with acid or alkali and enzymatic degradation lead to the conclusion that the bond is neither a phosphodiester such as nucleotidyl-(P-O-serine (or threonine) nor a phosphoramidate such as nucleotidyl4(P-N)amino acid. VPg-RNA can be iodinated by the end of polio genome RNA can now be described as VPg(Tyr-

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mentioning

confidence: 99%

“…Polio VPg is hydrophobic (1,2) and basic (net charge of +7 at pH 7.5, ref. 4) and has a molecular weight of 4000-6000 as determined by polyacrylamide gel electrophoresis (2,5,7).…”

mentioning

confidence: 99%

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O4-(5'-uridylyl)tyrosine is the bond between the genome-linked protein and the RNA of poliovirus.

Rothberg¹,

Harris²,

Nomoto³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

227

134

View full text Add to dashboard Cite

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“…Poliovirus (PV) is a positive strand ssRNA virus that produces dsRNA intermediates during viral replication (15), modified with 59 terminal Vpg protein (16), a characteristic feature of picornaviruses. It is generally accepted that picornaviruses are recognized by MDA5 but not RIG-I in infected cells, presumably due to the generation of this unusual dsRNA.…”

Section: W Hen Rna Viruses Infect Mammalian Cells Type I Ifnmentioning

confidence: 99%

“…In infected cells, picornaviruses efficiently generate long dsRNA, which is recognized by the cytoplasmic dsRNA sensor MDA5 (23). The 59 end of the PV genomic RNA is linked to a VPg protein (16), not to a 59-triphosphate, a major ligand for another cytoplasmic RNA sensor, RIG-I (24,25). Thus, we first tested, using the PVRtg mouse model (20), whether the mortality of PV-infected mice is affected by disruption of IPS-1 (Fig.…”

Section: Ticam-1 Is Essential For Protection Of Pvrtg Mice Against Pvmentioning

confidence: 99%

The TLR3/TICAM-1 Pathway Is Mandatory for Innate Immune Responses to Poliovirus Infection

Oshiumi

Okamoto

Fujii

et al. 2011

The Journal of Immunology

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Cytoplasmic and endosomal RNA sensors recognize RNA virus infection and signals to protect host cells by inducing type I IFN. The cytoplasmic RNA sensors, retinoic acid inducible gene I/melanoma differentiation-associated gene 5, actually play pivotal roles in sensing virus replication. IFN-β promoter stimulator-1 (IPS-1) is their common adaptor for IFN-inducing signaling. Toll/IL-1R homology domain-containing adaptor molecule 1 (TICAM-1), also known as TRIF, is the adaptor for TLR3 that recognizes viral dsRNA in the early endosome in dendritic cells and macrophages. Poliovirus (PV) belongs to the Picornaviridae, and melanoma differentiation-associated gene 5 reportedly detects replication of picornaviruses, leading to the induction of type I IFN. In this study, we present evidence that the TLR3/TICAM-1 pathway governs IFN induction and host protection against PV infection. Using human PVR transgenic (PVRtg) mice, as well as IPS-1−/− and TICAM-1−/− mice, we found that TICAM-1 is essential for antiviral responses that suppress PV infection. TICAM-1−/− mice in the PVRtg background became markedly susceptible to PV, and their survival rates were decreased compared with wild-type or IPS-1−/− mice. Similarly, serum and organ IFN levels were markedly reduced in TICAM-1−/−/PVRtg mice, particularly in the spleen and spinal cord. The sources of type I IFN were CD8α+/CD11c+ splenic dendritic cells and macrophages, where the TICAM-1 pathway was more crucial for PV-derived IFN induction than was the IPS-1 pathway in ex vivo and in vitro analyses. These data indicate that the TLR3/TICAM-1 pathway functions are dominant in host protection and innate immune responses against PV infection.

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Synthesis and Biological Evaluation of 7‐Deoxy Analogues of the Human Rhinovirus 3C Protease Inhibitor Thysanone

et al. 2013

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The synthesis of (±)‐7‐deoxythysanone and three analogues has been developed. The key oxa‐Pictet–Spengler reaction enabled the synthesis of the naphthopyran precursor, which could be readily converted to 7‐deoxythysanone and three related analogues. The biological activity of these compounds was also evaluated against HRV 3C protease, the results of which suggest that inhibition of the enzyme requires the presence of the 7‐oxa functionality.

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The location of the polio genome protein in viral RNAs and its implication for RNA synthesis

Cited by 265 publications

References 19 publications

O4-(5'-uridylyl)tyrosine is the bond between the genome-linked protein and the RNA of poliovirus.

O4-(5'-uridylyl)tyrosine is the bond between the genome-linked protein and the RNA of poliovirus.

The TLR3/TICAM-1 Pathway Is Mandatory for Innate Immune Responses to Poliovirus Infection

Synthesis and Biological Evaluation of 7‐Deoxy Analogues of the Human Rhinovirus 3C Protease Inhibitor Thysanone

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