Abstract
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.
Highlights
An acute viral infection can result in complete recovery of the host, death or establishment of persistence
We present evidence that ectromelia virus (ECTV) causes a persistent infection in some strains of disease-susceptible mice in which infectious virus was present in the bone marrow for several weeks post-infection
Infectious virus was isolated from resistant mice that had been subjected to sustained immunosuppression several weeks post-infection
Summary
An acute viral infection can result in complete recovery of the host, death or establishment of persistence. The OPV genus is generally believed to cause acute infections Some members such as ECTV [1,2,3,4,5,6,7], monkeypox virus (MPXV) [8], cowpox virus (CPXV) [8,9,10] and vaccinia virus (VACV) [11,12] have been reported to persist for several weeks or months after experimental infection in a variety of animal species that show no clinical signs of disease [13]. VARV causes smallpox in humans but the disease was successfully eradicated through vaccination more than 35 years ago [13] without any evidence of re-emergence, implying that it does not cause persistent infections
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
