Abstract
Infection of non-human primates (NHPs) such as rhesus and cynomolgus macaques with monkeypox virus (MPXV) or cowpox virus (CPXV) serve as models to study poxvirus pathogenesis and to evaluate vaccines and anti-orthopox therapeutics. Intravenous inoculation of macaques with high dose of MPXV (>1–2×107 PFU) or CPXV (>102 PFU) results in 80% to 100% mortality and 66 to 100% mortality respectively. Here we report that NHPs with positive detection of poxvirus antigens in immune cells by flow cytometric staining, especially in monocytes and granulocytes succumbed to virus infection and that early positive pox staining is a strong predictor for lethality. Samples from four independent studies were analyzed. Eighteen NHPs from three different experiments were inoculated with two different MPXV strains at lethal doses. Ten NHPs displayed positive pox-staining and all 10 NHPs reached moribund endpoint. In contrast, none of the three NHPs that survived anticipated lethal virus dose showed apparent virus staining in the monocytes and granulocytes. In addition, three NHPs that were challenged with a lethal dose of MPXV and received cidofovir treatment were pox-antigen negative and all three NHPs survived. Furthermore, data from a CPXV study also demonstrated that 6/9 NHPs were pox-antigen staining positive and all 6 NHPs reached euthanasia endpoint, while the three survivors were pox-antigen staining negative. Thus, we conclude that monitoring pox-antigen staining in immune cells can be used as a biomarker to predict the prognosis of virus infection. Future studies should focus on the mechanisms and implications of the pox-infection of immune cells and the correlation between pox-antigen detection in immune cells and disease progression in human poxviral infection.
Highlights
monkeypox virus (MPXV) and cowpox virus (CPXV) are members of the Orthopoxvirus family that includes variola virus (VARV), the causative agent of human smallpox and vaccinia virus (VACV)
Models of MPXV infection in rhesus or cynomolgus macaques have been used to evaluate anti-poxvirus drugs and vaccines because disease observed in macaques resembles that seen in humans
In the current in vivo non-human primates (NHPs) studies, we report for the first time that monocytes and granulocytes in the blood are the major cell populations that were pox-antigen positive measured by FACS
Summary
MPXV and CPXV are members of the Orthopoxvirus family that includes variola virus (VARV), the causative agent of human smallpox and vaccinia virus (VACV). After cessation of broad VACV immunization, MPXV infections are emerging as a public health concern. VARV or MPXV could be released as bioterrorist agents [3]. Such concerns have resulted in increasing effort to elucidate poxvirus pathogenesis and to develop anti-orthopox virus vaccines and drugs. Non-human primates (NHPs) infected with MPXV or CPXV serve as models of human orthopox viral disease [5,6,7,8]
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.
