Migration of the coronavirus replication complex from sites of RNA synthesis to sites of virion assembly
出版項
2000
說明
1 online resource (169 pages)
文字
text
無媒介
computer
成冊
online resource
附註
Source: Dissertations Abstracts International, Volume: 62-11, Section: B
Publisher info.: Dissertation/Thesis
Advisor: Denison, Mark R
Thesis (Ph.D.)--Vanderbilt University, 2000
Includes bibliographical references
The coronavirus genus of the Coronaviridae family includes viruses pathogenic to humans and domestic animals, causing diseases ranging from upper respiratory tract infection to encephalitis and hepatitis. Coronaviruses are enveloped and contain a 32kb genome of positive-sense RNA. Although coronavirus species have extensive sequence diversity in the genes encoding proteins required for virus entry, several regions within the replicase gene (gene 1) are highly conserved even among coronaviruses with distinct tropisms. This suggests that the post-entry process of coronavirus RNA synthesis is conserved among multiple coronavirus species. Yet, prior to this dissertation research, a replication complex had not been identified for any coronavirus, and it remained unclear whether viral RNA synthesis was mediated at the site of virion assembly or at an independent site. In addition, the role of cellular membranes and cytoskeletal elements in facilitating the post-entry steps in viral replication had not been determined. My dissertation work has demonstrated that coronavirus RNA synthesis occurs in multi-protein replication complexes at sites distinct from virion assembly and that viral nucleocapsids are delivered to assembly sites via migration of replication shuttle complexes. The migration results in separation of at least two gene 1 proteins from the RNA-containing shuttle complex, suggesting functional divergence of the two replicase protein populations after initial RNA synthesis. Shuttle complex relocalization to the coronavirus budding compartment (ERGIC) is concurrent with extensive rearrangement of intracellular membranes as well as with redistribution of the M assembly protein from the trans Golgi to the ERGIC. These steps precede a microtubule-dependent coalescence of replicase and assembly proteins in the ERGIC of multinucleated syncytia. Together these data have led to the development of a new model of how the distinct processes of coronavirus RNA synthesis and virion assembly combine to generate infectious progeny virions
Electronic reproduction. Ann Arbor, Mich. : ProQuest, 2021
