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Studies of Mumps Virus RNA Synthesis...

Briggs, Kelsey Rose,

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Studies of Mumps Virus RNA Synthesis and Immunogenicity /

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Studies of Mumps Virus RNA Synthesis and Immunogenicity // Kelsey Rose Briggs.
作者:	Briggs, Kelsey Rose,
面頁冊數:	1 electronic resource (197 pages)
附註:	Source: Dissertations Abstracts International, Volume: 83-08, Section: B.
Contained By:	Dissertations Abstracts International83-08B.
標題:	Virology. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28774709
ISBN:	9798780624073

Studies of Mumps Virus RNA Synthesis and Immunogenicity /
Briggs, Kelsey Rose,

Studies of Mumps Virus RNA Synthesis and Immunogenicity /Kelsey Rose Briggs. - 1 electronic resource (197 pages)

Source: Dissertations Abstracts International, Volume: 83-08, Section: B.

Mumps virus (MuV) is a highly contagious human pathogen in the Paramyxoviridae family. The hallmark symptom of mumps is the swelling of the parotid glands. Though clinical symptoms of mumps are often mild, severe neurological complications, such as meningitis and encephalitis, can occur (1). After the introduction of the mumps vaccine, cases dramatically decreased to less than 500 per year in the United States. However, there has been a resurgence of mumps in the last two decades, warranting a better understanding of the disease and virus (2). There are no approved anti-viral drugs available for mumps. Viral replication and transcription have become targets for therapeutics in recent years (3). This work seeks to better understand virus-host interactions and the role phosphorylation plays in RNA synthesis. It is well established that the MuV nucleoprotein (NP) and phosphoprotein (P) are highly phosphorylated by host kinases and that their phosphorylation status regulates viral transcription and replication (4, 5). However, many host kinase regulators remain unknown. In this study, we identify a novel virus-host interaction. We show that host kinase, ribosomal protein S6 kinase beta-1 (RPS6KB1), negatively regulates MuV growth via phosphorylation of the MuV phosphoprotein. We then provide novel evidence that the MuV large (L) protein is phosphorylated during in vitro infection and identify four putative phosphorylation sites within the polyribonucleotidyltransferase domain of L. Our work provides insight into phosphorylation as a regulator of MuV growth. MuV outbreaks are occurring in vaccinated populations, and clinical isolates sequenced from these outbreaks belong to a divergent genotype (genotype G) compared to the vaccine strain (genotype A), which questions the efficacy of the mumps component of the measles, mumps, and rubella (MMR) vaccine. (2). We examine the immunogenicity and longevity of recombinant genotype G-based vaccines and show that a third dose of a genotype G-based vaccine increases neutralizing titers toward the circulating outbreak strain of MuV. We identify a host kinase important for MuV replication, elucidate MuV polymerase phosphorylation, and seek to advance the development of a next generation MuV vaccine.

English

ISBN: 9798780624073Subjects--Topical Terms:

642304
Virology.
Subjects--Index Terms:

Large protein

Studies of Mumps Virus RNA Synthesis and Immunogenicity /
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520 $a Mumps virus (MuV) is a highly contagious human pathogen in the Paramyxoviridae family. The hallmark symptom of mumps is the swelling of the parotid glands. Though clinical symptoms of mumps are often mild, severe neurological complications, such as meningitis and encephalitis, can occur (1). After the introduction of the mumps vaccine, cases dramatically decreased to less than 500 per year in the United States. However, there has been a resurgence of mumps in the last two decades, warranting a better understanding of the disease and virus (2). There are no approved anti-viral drugs available for mumps. Viral replication and transcription have become targets for therapeutics in recent years (3). This work seeks to better understand virus-host interactions and the role phosphorylation plays in RNA synthesis. It is well established that the MuV nucleoprotein (NP) and phosphoprotein (P) are highly phosphorylated by host kinases and that their phosphorylation status regulates viral transcription and replication (4, 5). However, many host kinase regulators remain unknown. In this study, we identify a novel virus-host interaction. We show that host kinase, ribosomal protein S6 kinase beta-1 (RPS6KB1), negatively regulates MuV growth via phosphorylation of the MuV phosphoprotein. We then provide novel evidence that the MuV large (L) protein is phosphorylated during in vitro infection and identify four putative phosphorylation sites within the polyribonucleotidyltransferase domain of L. Our work provides insight into phosphorylation as a regulator of MuV growth. MuV outbreaks are occurring in vaccinated populations, and clinical isolates sequenced from these outbreaks belong to a divergent genotype (genotype G) compared to the vaccine strain (genotype A), which questions the efficacy of the mumps component of the measles, mumps, and rubella (MMR) vaccine. (2). We examine the immunogenicity and longevity of recombinant genotype G-based vaccines and show that a third dose of a genotype G-based vaccine increases neutralizing titers toward the circulating outbreak strain of MuV. We identify a host kinase important for MuV replication, elucidate MuV polymerase phosphorylation, and seek to advance the development of a next generation MuV vaccine.
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650 4 $a Immunology. $3 611031
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653 $a Vaccine
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720 1 $a He, Biao $e degree supervisor.
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