title: Cowpox virus infection of cynomolgus macaques as a model of hemorrhagic smallpox.
abstract: Hemorrhagic smallpox was a rare but severe manifestation of variola virus infection that resulted in nearly 100% mortality. Here we describe intravenous (IV) inoculation of cowpox virus Brighton Red strain in cynomolgus macaques (Macaca fascicularis) which resulted in disease similar in presentation to hemorrhagic smallpox in humans. IV inoculation of macaques resulted in a uniformly lethal disease within 12 days post-inoculation in two independent experiments. Clinical observations and hematological and histopathological findings support hemorrhagic disease. Cowpox virus replicated to high levels in blood (8.0-9.0 log(10) gene copies/mL) and tissues including lymph nodes, thymus, spleen, bone marrow, and lungs. This unique model of hemorrhagic orthopoxvirus infection provides an accessible means to further study orthopoxvirus pathogenesis and to identify virus-specific and nonspecific therapies. Such studies will serve to complement the existing nonhuman primate models of more classical poxviral disease.
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. johnsonreed@mail.nih.gov
authors.forename: Reed F
authors.initials: RF
authors.lastname: Johnson
authors.forename: Srikanth
authors.initials: S
authors.lastname: Yellayi
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Cann
authors.forename: Anthony
authors.initials: A
authors.lastname: Johnson
authors.forename: Alvin L
authors.initials: AL
authors.lastname: Smith
authors.forename: Jason
authors.initials: J
authors.lastname: Paragas
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Blaney
mesh_terms: D000818:Animals; D015605:Cowpox / Q000150:complications* / Q000276:immunology / Q000473:pathology*; D015608:Cowpox virus / Q000145:classification / Q000502:physiology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000276:immunology; D006470:Hemorrhage; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear; D008252:Macaca fascicularis; D012899:Smallpox / Q000150:complications*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D016207:Cytokines