TUMOR-NECROSIS-FACTOR AND THE PATHOGENESIS OF PICHINDE VIRUS-INFECTION IN GUINEA-PIGS

Pichinde virus (PIG) is a reticuloendothelial arenavirus of the New Wo rld tropics. A guinea pig passage-adapted strain of this virus (adPIC) is uniformly lethal for inbred guinea pigs, while the related, protot ype strain (PIC3739) has attenuated virulence. The abilities of adPIC and PIC3739 to induce tumor necrosis factor (TNF) in vivo and in cultu red macrophages were compared. Infection with adPIC, but not PIC3739, was associated with detectable serum TNF that peaked in week 2 of infe ction. Tumor necrosis factor was found in the spleens of adPIC- and PI C3739-infected animals in week 1 of infection; TNF alpha mRNA levels i n spleens and livers of adPIC infected animals increased and remained high throughout infection, whereas PIC3739-infected organs showed down regulation of TNF alpha mRNA late in infection. Peritoneal macrophage s explanted from adPIC-infected animals showed enhanced lipopolysaccha ride-inducible TNF production. Altered regulation of TNF production ma y play a role in the pathogenesis of guinea pig arenavirus disease.