دورية أكاديمية
أعرض في EDS

Molecular insights into type I interferon suppression and enhanced pathogenicity by species B human adenoviruses B7 and B14.

التفاصيل البيبلوغرافية
العنوان: Molecular insights into type I interferon suppression and enhanced pathogenicity by species B human adenoviruses B7 and B14.
المؤلفون: Graves D; Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada., Akkerman N; Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada., Fulham L; Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada., Helwer R; Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada., Pelka P; Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
المصدر: MBio [mBio] 2024 Aug 14; Vol. 15 (8), pp. e0103824. Date of Electronic Publication: 2024 Jun 28.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Society for Microbiology
مواضيع طبية MeSH: Adenoviruses, Human*/genetics , Adenoviruses, Human*/pathogenicity , Adenoviruses, Human*/physiology , Adenoviruses, Human*/immunology , Interferon Type I*/immunology , Interferon Type I*/metabolism , Interferon Type I*/genetics, Humans ; STAT2 Transcription Factor/metabolism ; STAT2 Transcription Factor/genetics ; Immunity, Innate ; RNA Polymerase II/metabolism ; RNA Polymerase II/genetics ; Signal Transduction ; Adenovirus Infections, Human/virology ; Adenovirus Infections, Human/immunology ; Virulence ; Host-Pathogen Interactions/immunology ; Animals ; Promoter Regions, Genetic ; Immune Evasion ; A549 Cells
مستخلص: Human adenoviruses (HAdVs) are small DNA viruses that generally cause mild disease. Certain strains, particularly those belonging to species B HAdVs, can cause severe pneumonia and have a relatively high mortality rate. Little is known about the molecular aspects of how these highly pathogenic species affect the infected cell and how they suppress innate immunity. The present study provides molecular insights into how species B adenoviruses suppress the interferon signaling pathway. Our study shows that these viruses, unlike HAdV-C2, are resistant to type I interferon. This resistance likely arises due to the highly efficient suppression of interferon-stimulated gene expression. Unlike in HAdV-C2, HAdV-B7 and B14 sequester STAT2 and RNA polymerase II from interferon-stimulated gene promoters in infected cells. This results in suppressed interferon- stimulated gene activation. In addition, we show that RuvBL1 and RuvBL2, cofactors important for RNA polymerase II recruitment to promoters and interferon-stimulated gene activation, are redirected to the cytoplasm forming high molecular weight complexes that, likely, are unable to associate with chromatin. Proteomic analysis also identified key differences in the way these viruses affect the host cell, providing insights into species B-associated high pathogenicity. Curiously, we observed that at the level of protein expression changes to the infected cell, HAdV-C2 and B7 were more similar than those of the same species, B7 and B14. Collectively, our study represents the first such study of innate immune suppression by the highly pathogenic HAdV-B7 and B14, laying an important foundation for future investigations.IMPORTANCEHuman adenoviruses form a large family of double-stranded DNA viruses known for a variety of usually mild diseases. Certain strains of human adenovirus cause severe pneumonia leading to much higher mortality and morbidity than most other strains. The reasons for this enhanced pathogenicity are unknown. Our study provides a molecular investigation of how these highly pathogenic strains might inactivate the interferon signaling pathway, highlighting the lack of sensitivity of these viruses to type I interferon in general while providing a global picture of how viral changes in cellular proteins drive worse disease outcomes.
Competing Interests: The authors declare no conflict of interest.
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معلومات مُعتمدة: PJT-173376 Canadian Government | Canadian Institutes of Health Research (CIHR)
فهرسة مساهمة: Keywords: RuvBL1; RuvBL2; adenovirus; interferon; transcription
المشرفين على المادة: 0 (Interferon Type I)
0 (STAT2 Transcription Factor)
EC 2.7.7.- (RNA Polymerase II)
0 (STAT2 protein, human)
تواريخ الأحداث: Date Created: 20240628 Date Completed: 20240814 Latest Revision: 20240816
رمز التحديث: 20240816
مُعرف محوري في PubMed: PMC11323573
DOI: 10.1128/mbio.01038-24
PMID: 38940561
قاعدة البيانات: MEDLINE
الوصف
تدمد:2150-7511
DOI:10.1128/mbio.01038-24