자료유형  

 학위논문

Control Number  

0016931802

International Standard Book Number  

9798379711573

Dewey Decimal Classification Number  

576.6

Main Entry-Personal Name  

Lopez-Astacio, Robert Alexis.

Publication, Distribution, etc. (Imprint  

[S.l.] : Cornell University., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(181 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 84-12, Section: B.

General Note  

Advisor: Parrish, Colin.

Dissertation Note  

Thesis (Ph.D.)--Cornell University, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Restrictions on Access Note  

This item must not be added to any third party search indexes.

Summary, Etc.  

요약Parvoviruses, including feline (FPV) and canine parvovirus (CPV), are among the smallest and structurally simplest viruses described, both in their genome composition as well as their overall icosahedral capsid structure. Their capsids are composed of variants of a single structural protein that controls many of the required steps involved in replication, and for the interaction with many host-derived ligands and molecules, including cellular receptors and antibodies. Despite their apparent simplicity, FPV and CPV replication and spread involve complex and dynamic interactions that lead to broad and variable host ranges, rapid adaptation, successful sustained transmission, host immunity evasion, and a long evolutionary trajectory. In this dissertation I have used FPV and CPV as models to better understand capsid structures and functions, to describe the genetic variation in virus populations as a result of their many and intricate interactions with host-derived molecules such as receptors and antibodies, and to describe and characterize their overall evolutionary history. I found that CPV capsids acquire mutations during their replication, and functional mutations are selected in the face of neutralizing antibodies. Those selected residues fell within or were close to antibody footprints, and they generally avoided receptor binding sites despite the overlapping of those two. Antibody-selected mutations in capsids result in decreased binding to the antibodies, showing that those are escape mutations. Additionally, I found that those antibody escape mutations were still mostly restricted to the same general residues in the viral capsid when using mutated versions of the antibodies. Many of these in vitro-selected mutations are also found in natural isolates, suggesting they are linked to the natural variants that evade the host-immune system.Despite the long evolutionary trajectory of FPV, I found that all FPV strains are ~99% identical in nucleotide sequence. I was also able to reveal the landscape of mutations that have become widespread in the FPV genomes during 57 years of its evolutionary history in cats and other susceptible hosts, and I compared the results from FPV to what has been seen for CPV. I also found that ~66% of the substitutions that became widespread in CPV genomes are present at low frequencies among the FPV natural variants, and also showed that most of the FPV vaccines currently in use are derived from one virus first isolated in the 1960s. The FPV-like viruses evolved at similar rates to CPV-derived viruses in their different hosts, but most substitutions in FPV within the capsid protein gene were silent changes. The small number of coding changes in the FPV lineage do not appear to alter the known antigenic epitopes of parvoviruses, suggesting the continued efficaciousness of the 60-year-old vaccines in cats.The results of this dissertation provide new information that is immediately relevant to the emergence of new viruses, and they also provide new insights into how viruses evolve, adapt, overcome species barriers, and persist in natural reservoirs, as well as revealing the complicated and sophisticated roles of parvovirus capsids despite their seeming simplicity.

Subject Added Entry-Topical Term  

Virology.

Subject Added Entry-Topical Term  

Immunology.

Subject Added Entry-Topical Term  

Biology.

Subject Added Entry-Topical Term  

Evolution & development.

Index Term-Uncontrolled  

Antibodies

Index Term-Uncontrolled  

Capsid structure

Index Term-Uncontrolled  

Mutations

Index Term-Uncontrolled  

Parvoviruses

Index Term-Uncontrolled  

Antibody footprints

Added Entry-Corporate Name  

Cornell University Biomedical and Biological Sciences

Host Item Entry  

Dissertations Abstracts International. 84-12B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:639498