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Innate Immune Antagonism by Diverse Coronavirus Phosphodiesterases

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서명/저자사항Innate Immune Antagonism by Diverse Coronavirus Phosphodiesterases.
개인저자Goldstein, Stephen A.
단체저자명University of Pennsylvania. Cell and Molecular Biology.
발행사항[S.l.]: University of Pennsylvania., 2019.
발행사항Ann Arbor: ProQuest Dissertations & Theses, 2019.
형태사항170 p.
기본자료 저록Dissertations Abstracts International 81-02B.
Dissertation Abstract International
ISBN9781085561716
학위논문주기Thesis (Ph.D.)--University of Pennsylvania, 2019.
일반주기 Source: Dissertations Abstracts International, Volume: 81-02, Section: B.
Advisor: Weiss, Susan R.
이용제한사항This item must not be sold to any third party vendors.
요약Coronaviruses comprise a large family of viruses within the order Nidovirales containing single-stranded positive-sense RNA genomes of 27-32 kilobases. Divided into four genera (alpha, beta, gamma, delta) and multiple newly defined subgenera, coronaviruses include a number of important human and livestock pathogens responsible for a range of diseases. Historically, human coronaviruses OC43 and 229E have been associated with up to 30% of common colds, while the 2002 emergence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) first raised the specter of these viruses as possible pandemic agents. Although the SARS-CoV pandemic was quickly contained and the virus has not returned, the 2012 discovery of Middle East respiratory syndrome-associated coronavirus (MERS-CoV) once again elevated coronaviruses to a list of global public health threats. The genetic diversity of these viruses has resulted in their utilization of both conserved and unique mechanisms of interaction with infected host cells. Like all viruses, coronaviruses encode multiple mechanisms for evading, suppressing, or otherwise circumventing host antiviral responses. Specifically, our lab has studied coronavirus interactions with antiviral pathways activated by the presence of cytoplasmic viral double-stranded RNA (dsRNA) such as OAS-RNase L and interferons (IFN). Previous work from our lab demonstrated that the murine coronavirus mouse hepatitis virus (MHV) uses a phosphodiesterase (PDE) to suppress RNase L activation. We have also now shown that additional viruses within Nidovirales encode similar PDEs that suppress RNase L activation in the context of chimeric MHV, and that a PDE encoded by MERS-CoV, the NS4b accessory protein, inhibits RNase L in its native context. I have further shown that MERS-CoV NS4b is a unique PDE with additional functions inhibiting the IFN response, a role dependent on both nuclear localization and its catalytic activity.
일반주제명Virology.
Microbiology.
Immunology.
언어영어
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