Tumor Necrosis Factor and the Pathogenesis of Pichinde Virus Infection in Guinea Pigs

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  • 1 Department of Pathology, University of Texas Medical Branch, Galveston, Texas

Pichinde virus (PIC) is a reticuloendothelial arenavirus of the New World tropics. A guinea pig passage–adapted strain of this virus (adPIC) is uniformly lethal for inbred guinea pigs, while the related, prototype strain (PIC3739) has attenuated virulence. The abilities of adPIC and PIC3739 to induce tumor necrosis factor (TNF) in vivo and in cultured macrophages were compared. Infection with adPIC, but not PIC3739, was associated with detectable serum TNF that peaked in week 2 of infection. Tumor necrosis factor was found in the spleens of adPIC- and PIC3739-infected animals in week 1 of infection ; TNFα mRNA levels in spleens and livers of adPIC infected animals increased and remained high throughout infection, whereas PIC3739-infected organs showed down regulation of TNFα mRNA late in infection. Peritoneal macrophages explanted from adPIC-infected animals showed enhanced lipopolysaccharide-inducible TNF production. Altered regulation of TNF production may play a role in the pathogenesis of guinea pig arenavirus disease.

Author Notes

Financial support: This work was supported by U.S. Army Contract DAMD 17-90-Z-0011 and by the James W. McLaughlin Fellowship Fund (JFA).

Authors' addresses: Judith F. Aronson and Norbert K. Herzog, Department of Pathology, F-09, University of Texas Medical Branch, Galveston, TX 77555-0609. Thomas R. Jerrells, Department of Cellular Biology and Anatomy, Louisiana State University Medical Center, Shreveport, LA 71130.

Reprint requests: Judith F. Aronson, Department of Pathology, F-09, University of Texas Medical Branch, Galveston, TX 77555-0609.

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