期刊论文详细信息
PLoS Pathogens
Diminished Reovirus Capsid Stability Alters Disease Pathogenesis and Littermate Transmission
Courtney A. Copeland1  Judy J. Brown1  James B. Atkinson1  Joshua D. Doyle1  Kelli L. Boyd2  Jennifer E. Stencel-Baerenwald2  Jillian P. Rhoads2  Terence S. Dermody2 
[1] Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America;Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
关键词: Viral packaging;    Heart;    Viral replication;    Cytokines;    Gastrointestinal tract;    Microbial mutation;    Virions;    Pathogenesis;   
DOI  :  10.1371/journal.ppat.1004693
学科分类:生物科学(综合)
来源: Public Library of Science
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【 摘 要 】

Reovirus is a nonenveloped mammalian virus that provides a useful model system for studies of viral infections in the young. Following internalization into host cells, the outermost capsid of reovirus virions is removed by endosomal cathepsin proteases. Determinants of capsid disassembly kinetics reside in the viral σ3 protein. However, the contribution of capsid stability to reovirus-induced disease is unknown. In this study, we found that mice inoculated intramuscularly with a serotype 3 reovirus containing σ3-Y354H, a mutation that reduces viral capsid stability, succumbed at a higher rate than those infected with wild-type virus. At early times after inoculation, σ3-Y354H virus reached higher titers than wild-type virus at several sites within the host. Animals inoculated perorally with a serotype 1 reassortant reovirus containing σ3-Y354H developed exaggerated myocarditis accompanied by elaboration of pro-inflammatory cytokines. Surprisingly, unchallenged littermates of mice infected with σ3-Y354H virus displayed higher titers in the intestine, heart, and brain than littermates of mice inoculated with wild-type virus. Together, these findings suggest that diminished capsid stability enhances reovirus replication, dissemination, lethality, and host-to-host spread, establishing a new virulence determinant for nonenveloped viruses.

【 授权许可】

CC BY   

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