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Identification and Comparison of SARS-CoV-2 Deletion Variants in Cell Cultures, Rodents, and Humans
Identification and Comparison of SARS-CoV-2 Deletion Variants in Cell Cultures, Rodents, and Humans
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105139
- ISBN
- 9798291587843
- DDC
- 574.191
- 저자명
- Jiang, Nan.
- 서명/저자
- Identification and Comparison of SARS-CoV-2 Deletion Variants in Cell Cultures, Rodents, and Humans
- 발행사항
- [Sl] : The University of Wisconsin - Madison, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 197 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-03, Section: B.
- 주기사항
- Advisor: Yin, John.
- 학위논문주기
- Thesis (Ph.D.)--The University of Wisconsin - Madison, 2025.
- 초록/해제
- 요약Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generates defective viral genomes (DVGs) through internal deletions, which can influence viral replication, immune responses, and evolutionary dynamics. Despite their prevalence in coronaviruses, the biological significance and system-specific characteristics of SARS-CoV-2 DVGs remain poorly understood. In this thesis, I optimized and validated a bioinformatics pipeline to detect deletion variants from multiplex-PCR sequencing data, removing over 99% of false positives while preserving true events. This framework was applied to clinical samples from asymptomatic, symptomatic, mild, and severe COVID-19 cases, revealing that symptomatic patients harbored significantly higher DVG frequencies, longer deletions, and enrichment for deletions interrupting replication and packaging signals. Extending these analyses to persistent infection models (longitudinally sampled patients, immunodeficient IL2RG knockout hamsters, and serially passaged SARS-CoV-2 in Vero E6 cells) demonstrated that DVG frequencies and compositions fluctuated over time, often in parallel with single-nucleotide variant (SNV) changes. Across all systems, deletions retaining both replication and packaging signals were enriched beyond random expectation, although system-specific patterns emerged, including longer tissue-associated deletions in hamsters and shorter, less diverse deletions in vitro. These results highlight both conserved and context-dependent features of SARS-CoV-2 DVGs, advancing understanding of their evolutionary and functional roles. The findings lay a foundation for mechanistic studies on DVG evolution and translational applications such as therapeutic interfering particles for controlling SARS-CoV-2 infection.
- 일반주제명
- Biophysics
- 일반주제명
- Virology
- 일반주제명
- Bioinformatics
- 일반주제명
- Cellular biology
- 일반주제명
- Genetics
- 기타저자
- The University of Wisconsin - Madison Biophysics
- 기본자료저록
- Dissertations Abstracts International. 87-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798291587843
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574.191
■1001 ▼aJiang, Nan.
■24510▼aIdentification and Comparison of SARS-CoV-2 Deletion Variants in Cell Cultures, Rodents, and Humans
■260 ▼a[Sl]▼bThe University of Wisconsin - Madison▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a197 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-03, Section: B.
■500 ▼aAdvisor: Yin, John.
■5021 ▼aThesis (Ph.D.)--The University of Wisconsin - Madison, 2025.
■520 ▼aSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generates defective viral genomes (DVGs) through internal deletions, which can influence viral replication, immune responses, and evolutionary dynamics. Despite their prevalence in coronaviruses, the biological significance and system-specific characteristics of SARS-CoV-2 DVGs remain poorly understood. In this thesis, I optimized and validated a bioinformatics pipeline to detect deletion variants from multiplex-PCR sequencing data, removing over 99% of false positives while preserving true events. This framework was applied to clinical samples from asymptomatic, symptomatic, mild, and severe COVID-19 cases, revealing that symptomatic patients harbored significantly higher DVG frequencies, longer deletions, and enrichment for deletions interrupting replication and packaging signals. Extending these analyses to persistent infection models (longitudinally sampled patients, immunodeficient IL2RG knockout hamsters, and serially passaged SARS-CoV-2 in Vero E6 cells) demonstrated that DVG frequencies and compositions fluctuated over time, often in parallel with single-nucleotide variant (SNV) changes. Across all systems, deletions retaining both replication and packaging signals were enriched beyond random expectation, although system-specific patterns emerged, including longer tissue-associated deletions in hamsters and shorter, less diverse deletions in vitro. These results highlight both conserved and context-dependent features of SARS-CoV-2 DVGs, advancing understanding of their evolutionary and functional roles. The findings lay a foundation for mechanistic studies on DVG evolution and translational applications such as therapeutic interfering particles for controlling SARS-CoV-2 infection.
■590 ▼aSchool code: 0262.
■650 4▼aBiophysics
■650 4▼aVirology
■650 4▼aBioinformatics
■650 4▼aCellular biology
■650 4▼aGenetics
■653 ▼aDeletion variants
■653 ▼aDefective viral genomes
■653 ▼aEvolutionary dynamics
■690 ▼a0786
■690 ▼a0720
■690 ▼a0715
■690 ▼a0379
■690 ▼a0369
■71020▼aThe University of Wisconsin - Madison▼bBiophysics.
■7730 ▼tDissertations Abstracts International▼g87-03B.
■790 ▼a0262
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17359572▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
