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: Reed F Johnson, Srikanth Yellayi, Jennifer A Cann, Anthony Johnson, Alvin L Smith, Jason Paragas, Peter B Jahrling, Joseph E Blaney
• Journal: Virology (Virology) Vol. 418 Issue 2 Pg. 102-12 (Sep 30 2011) ISSN: 1096-0341 [Electronic] United States
• PMID: 21840027 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Cytokines

Topics

• Animals
• Cowpox (complications, immunology, pathology)
• Cowpox virus (classification, physiology)
• Cytokines (genetics, metabolism)
• Disease Models, Animal
• Gene Expression Regulation (immunology)
• Hemorrhage
• Immunity, Innate
• Leukocytes, Mononuclear
• Macaca fascicularis
• Smallpox (complications)
• Viral Load
• Virus Replication