Molecular Cloning and Sequence Analysis of the Mumps Virus Gene Encoding the P Protein: Mumps Virus P Gene Is Monocistronic

Takeuchi, Kaoru; Hishiyama, Michiko; Yamada, Akio; Sugiura, Akira

doi:10.1099/0022-1317-69-8-2043

Cited by 35 publications

(13 citation statements)

References 25 publications

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“…Early peptide mapping data obtained for the P and "C-like" proteins of two other paramyxoviruses, Newcastle disease virus (NDV) and mumps virus, suggested that both proteins are encoded by the same reading frame (Collins et al, 1982;Herrler and Compans, 1982). Recently the NDV and mumps virus P genes have been sequenced and found to contain one open reading frame (Sato et al, 1987;McGinnes et al, 1988;Takeuchi et al, 1988) from which it has been suggested that both the P and "C-like" proteins are derived, with the "C-like" protein arising from initiation at an internal AUG codon (McGinnes et al, 1988). SV5 is therefore seemingly unique among paramyxoviruses in having two mRNAs transcribed from the P gene.…”

Section: Discussionmentioning

confidence: 99%

Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5

Thomas¹,

Lamb²,

Paterson³

1988

Cell

342

246

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The "P" gene of the paramyxovirus SV5 encodes two known proteins, P (Mr approximately equal to 44,000) and V (Mr approximately equal to 24,000). The complete nucleotide sequence of the "P" gene has been obtained and is found to contain two open reading frames, neither of which is large enough to encode the P protein. We have shown that the P and V proteins are translated from two mRNAs that differ by the presence of two nontemplated G residues in the P mRNA. These two additional nucleotides convert the two open reading frames to one of 392 amino acids. The P and V proteins are amino coterminal and have 164 amino acids in common. The unique C terminus of V consists of a cysteine-rich region that resembles a cysteine-rich metal binding domain. An open reading frame that contains this cysteine-rich region exists in all other paramyxovirus "P" gene sequences examined, which suggests that it may have important biological significance.

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Section: Discussionmentioning

confidence: 99%

Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5

Thomas¹,

Lamb²,

Paterson³

1988

Cell

342

246

View full text Add to dashboard Cite

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“…MuV is an enveloped single negative strand RNA virus that belongs to the genus Rubulavirus in the family Paramyxoviridae [1, 2]. MuV particles consist of seven proteins, N, P, M, F, SH, HN and L [3, 4]. V protein, which is encoded by P gene, is a nonstructural protein, and it strongly inhibits interferon (IFN) signal transduction, resulting in shutoff of the IFN-induced host antiviral response [5].…”

Section: Introductionmentioning

confidence: 99%

Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production

et al. 2016

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Stress granules (SGs) are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV) induced SGs depending on activation of protein kinase R (PKR). MuV infection strongly induced interferon (IFN)-λ1, 2 and 3, and IFN-β through activation of IFN regulatory factor 3 (IRF3) via retinoic acid inducible gene-I (RIG-I) and the mitochondrial antiviral signaling (MAVS) pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen-1, and significantly increased the levels of MuV-induced IFN-λ1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-λ1) mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection.

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“…The RNA genome associates with NP to form the helical ribonucleoprotein (RNP), which protects the genome from degradation and serves as the template for RNA synthesis. The NP also associates with the phosphoprotein (P) and indirectly with the large protein (L), in which P and L form the viral RNA-dependent RNA polymerase (vRdRp) (5). The vRdRp uses NP-encapsidated RNA as a template for both replication of the vRNA genome and production of mRNA (2).…”

mentioning

confidence: 99%

Roles of Phosphorylation of the Nucleocapsid Protein of Mumps Virus in Regulating Viral RNA Transcription and Replication

Zengel

Pickar

et al. 2015

J Virol

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Mumps virus (MuV) is a paramyxovirus with a negative-sense nonsegmented RNA genome. The viral RNA genome is encapsidated by the nucleocapsid protein (NP) to form the ribonucleoprotein (RNP), which serves as a template for transcription and replication. In this study, we investigated the roles of phosphorylation sites of NP in MuV RNA synthesis. Using radioactive labeling, we first demonstrated that NP was phosphorylated in MuV-infected cells. Using both liquid chromatography-mass spectrometry (LC-MS) and in silico modeling, we identified nine putative phosphorylated residues within NP. We mutated these nine residues to alanine. Mutation of the serine residue at position 439 to alanine (S439A) was found to reduce the phosphorylation of NP in transfected cells by over 90%. The effects of these mutations on the MuV minigenome system were examined. The S439A mutant was found to have higher activity, four mutants had lower activity, and four mutants had similar activity compared to wild-type NP. MuV containing the S439A mutation had 90% reduced phosphorylation of NP and enhanced viral RNA synthesis and viral protein expression at early time points after infection, indicating that S439 is the major phosphorylation site of NP and its phosphorylation plays an important role in downregulating viral RNA synthesis. IMPORTANCEMumps virus (MuV), a paramyxovirus, is an important human pathogen that is reemerging in human populations. Nucleocapsid protein (NP) of MuV is essential for viral RNA synthesis. We have identified the major phosphorylation site of NP. We have found that phosphorylation of NP plays a critical role in regulating viral RNA synthesis. The work will lead to a better understanding of viral RNA synthesis and possible novel targets for antiviral drug development. Mumps virus (MuV) infects humans, causing acute infection with hallmark enlargement of the parotid gland (1). Before widespread vaccination in the late 1960s, mumps was the leading cause of aseptic meningitis and caused deafness in children (2). Although vaccination has greatly reduced the number of infections, large outbreaks have occurred recently in vaccinated populations. The largest recent outbreak in the United States originated at a university in Iowa in 2006, where over 5,000 cases were reported, compared to approximately 250 cases per year in the preceding years (3). In 2014, there were over 1,100 cases of mumps reported, mainly centered around universities (4). At least 90% of the individuals infected received the measles, mumps, and rubella (MMR) vaccine, and the majority of people received two doses (3). New strategies to control these outbreaks are needed. Understanding the roles of each MuV protein in virus replication and pathogenesis will aid development of countermeasures for MuV.Mumps virus (MuV) is a member of the family Paramyxoviridae in the genus Rubulavirus (1). It has a negative-sense, nonsegmented RNA genome of 15,384 nucleotides. The genome is comprised of seven transcriptional units that encode nine viral proteins i...

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Molecular Cloning and Sequence Analysis of the Mumps Virus Gene Encoding the P Protein: Mumps Virus P Gene Is Monocistronic

Cited by 35 publications

References 25 publications

Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5

Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5

Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production

Roles of Phosphorylation of the Nucleocapsid Protein of Mumps Virus in Regulating Viral RNA Transcription and Replication

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