A mouse model of lethal infection for evaluating prophylactics and therapeutics against Monkeypox virus.
Monkeypox virus (MPXV) is an orthopoxvirus closely related to variola, the etiological agent of smallpox. In humans, MPXV causes a disease similar to smallpox and is considered to be an emerging infectious disease. Moreover, the use of MPXV for bioterroristic/biowarfare activities is of significant concern. Available small animal models of human monkeypox have been restricted to mammals with poorly defined biologies that also have limited reagent availability. We have established a murine MPXV model utilizing the STAT1-deficient C57BL/6 mouse. Here we report that a relatively low-dose intranasal (IN) infection induces 100% mortality in the stat1(-)(/)(-) model by day 10 postinfection with high infectious titers in the livers, spleens, and lungs of moribund animals. Vaccination with modified vaccinia virus Ankara (MVA) followed by a booster vaccination is sufficient to protect against an intranasal MPXV challenge and induces an immune response more robust than that of a single vaccination. Furthermore, antiviral treatment with CMX001 (HDP-cidofovir) and ST-246 protects when administered as a regimen initiated on the day of infection. Thus, the stat1(-)(/)(-) model provides a lethal murine platform for evaluating therapeutics and for investigating the immunological and pathological responses to MPXV infection.
Department of Molecular Microbiology and Immunology, Saint Louis University Medical School, 1100 S. Grand Blvd., St Louis, MO 63104, USA.
Jennifer
J
Stabenow
R Mark
RM
Buller
Jill
J
Schriewer
Cheri
C
West
John E
JE
Sagartz
Scott
S
Parker
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D001549:Benzamides; D003596:Cytosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D054833:Isoindoles; D008099:Liver / Q000821:virology; D008168:Lung / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D045908:Mpox, Monkeypox / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control*; D008993:Monkeypox virus / Q000187:drug effects* / Q000472:pathogenicity*; D063065:Organophosphonates / Q000627:therapeutic use; D050794:STAT1 Transcription Factor / Q000172:deficiency; D012900:Smallpox Vaccine / Q000276:immunology; D013154:Spleen / Q000821:virology; D016019:Survival Analysis; D016896:Treatment Outcome; D014616:Vaccinia virus / Q000276:immunology; D019562:Viral Load; D010797:Phthalimides
D000998:Antiviral Agents; D001549:Benzamides; D003596:Cytosine; D054833:Isoindoles; D063065:Organophosphonates; D050794:STAT1 Transcription Factor; D012900:Smallpox Vaccine; C494080:Stat1 protein, mouse; C525733:brincidofovir; C505045:tecovirimat; D010797:Phthalimides