Evidence for Persistence of Ectromelia Virus in Inbred Mice, Recrudescence Following Immunosuppression and Transmission to Naïve Mice

PLoS Pathogens

Isaac G. Sakala¹  Geeta Chaudhri¹  Preethi Eldi¹  Gunasegaran Karupiah¹  Anthony A. Scalzo²  Robert M. Buller³  Timothy P. Newsome⁴ 

[1] Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australia;Immunology and Virology Program, Centre for Ophthalmology & Visual Science, The Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia;Saint Louis University Health Sciences Center, Department of Molecular Microbiology and Immunology, St Louis, Missouri, United States of America;School of Molecular Bioscience, University of Sydney, Sydney, Australia

关键词: T cells;    Cytotoxic T cells;    Viral persistence;    latency;    Mammalian genomics;    Viral genomics;    Viral load;    Immune response;    Immune suppression;   

DOI  :  10.1371/journal.ppat.1005342

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Orthopoxviruses (OPV), including variola, vaccinia, monkeypox, cowpox and ectromelia viruses cause acute infections in their hosts. With the exception of variola virus (VARV), the etiological agent of smallpox, other OPV have been reported to persist in a variety of animal species following natural or experimental infection. Despite the implications and significance for the ecology and epidemiology of diseases these viruses cause, those reports have never been thoroughly investigated. We used the mouse pathogen ectromelia virus (ECTV), the agent of mousepox and a close relative of VARV to investigate virus persistence in inbred mice. We provide evidence that ECTV causes a persistent infection in some susceptible strains of mice in which low levels of virus genomes were detected in various tissues late in infection. The bone marrow (BM) and blood appeared to be key sites of persistence. Contemporaneous with virus persistence, antiviral CD8 T cell responses were demonstrable over the entire 25-week study period, with a change in the immunodominance hierarchy evident during the first 3 weeks. Some virus-encoded host response modifiers were found to modulate virus persistence whereas host genes encoded by the NKC and MHC class I reduced the potential for persistence. When susceptible strains of mice that had apparently recovered from infection were subjected to sustained immunosuppression with cyclophosphamide (CTX), animals succumbed to mousepox with high titers of infectious virus in various organs. CTX treated index mice transmitted virus to, and caused disease in, co-housed naïve mice. The most surprising but significant finding was that immunosuppression of disease-resistant C57BL/6 mice several weeks after recovery from primary infection generated high titers of virus in multiple tissues. Resistant mice showed no evidence of a persistent infection. This is the strongest evidence that ECTV can persist in inbred mice, regardless of their resistance status.

【 授权许可】

CC BY