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The Roles of Viral and Host Proteins in Influenza A Virus Assembly and Budding in Infected Cells
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | The Roles of Viral and Host Proteins in Influenza A Virus Assembly and Budding in Infected Cells. |
| 개인저자 | Bedi, Sukhmani Kaur. |
| 단체저자명 | University of Michigan. Microbiology & Immunology. |
| 발행사항 | [S.l.]: University of Michigan., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 137 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-05B. Dissertation Abstract International |
| ISBN | 9781687934352 |
| 학위논문주기 | Thesis (Ph.D.)--University of Michigan, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Advisor: Ono, Akira. |
| 이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
| 요약 | Influenza A Virus (IAV) assembly at the plasma membrane of infected cells is a complicated process that is orchestrated by at least five viral components: hemagglutinin (HA), neuraminidase (NA), matrix (M1), the ion channel M2, and viral ribonucleoprotein complexes (vRNPs). While the roles of these individual viral components during IAV assembly have been described before, the precise nature and sequence of interactions between viral proteins during IAV assembly are not completely understood. In addition, very few host factors that are involved in IAV assembly have been identified. The goal of this thesis is to better define the role of viral and host factors in IAV assembly. To do so, a strategy that involves comparison between cell types that support IAV assembly (permissive) and cell types that do not (non-permissive) has been employed. This comparison allows for identification of viral-viral and viral-host interactions that regulate IAV assembly in host cells.In this thesis, the primary human monocyte-derived macrophages (MDM) has been identified as a cell type that is non-permissive to IAV assembly. In comparison with a cell type that is permissive to IAV assembly, MDM are efficient at supporting the early steps of the IAV life cycle but fail to support assembly of nascent particles. A more thorough analysis of the IAV assembly process revealed that MDM are defective at supporting a discrete step in IAV assembly: association between the viral proteins HA and M2 at the plasma membrane. In addition, the association between HA and M2 likely precedes particle assembly in cells and hence, is an essential step for initiation of virus particle assembly. As for the host factors involved in IAV assembly, IAV particle assembly is restored in MDM upon disruption of the actin cytoskeleton. Hence, the actin cytoskeleton plays a negative role in IAV assembly in a cell-type-dependent manner. In addition, the actin cytoskeleton suppresses IAV assembly in MDM likely by restricting the association of M2 with HA. Data in this thesis further indicate that both linear and branched actin filaments contribute to suppression of HA-M2 association in MDM. Overall, in this thesis, key viral and host factors that regulate assembly of nascent IAV particles have been identified. This information will potentially aid in development of new antiviral strategies that specifically target IAV assembly. |
| 일반주제명 | Microbiology. Cellular biology. Virology. |
| 언어 | 영어 |
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