The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/5/1555/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 10, May 17, 1999 1555-1564

Articles

Noncytopathic Clearance of Lymphocytic Choriomeningitis Virus from the Hepatocyte

Luca G. Guidotti*, Persephone Borrow{ddagger}, Amy Brown*, Heike McClary*, Rick Koch*, and Francis V. Chisari*

From the * Department of Molecular and Experimental Medicine and the {ddagger} Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037

We have previously shown that interferon and tumor necrosis factor noncytopathically abolish hepatitis B virus (HBV) replication from the hepatocyte and kidney tubular epithelial cells in vivo. Here we show that a persistent lymphocytic choriomeningitis virus (LCMV) infection is cleared from the hepatocyte noncytopathically when the same cytokines are induced in the liver by antigen-nonspecific stimuli. These results indicate that, like HBV, LCMV is also susceptible to intracellular inactivation by cytokine-induced antiviral mechanisms that are operative in the hepatocyte. In contrast, LCMV is not cleared from intrahepatic nonparenchymal cells or splenocytes, indicating that, unlike the hepatocyte, these cells do not produce the factors required to inactivate LCMV. Antiviral mechanisms like these may have evolved to maintain the functional integrity of vital organs in the face of massive infection.

Key Words: lymphocytic choriomeningitis virus • noncytopathic clearance • hepatocyte • cytokines

Address correspondence to Luca G. Guidotti, The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: 619-784-2758; Fax: 619-784-2960; E-mail: guidotti{at}scripps.edu

P. Borrow's present address is The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, UK.

Abbreviations used: APP, acute phase protein; ARM, Armstrong strain; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HBV, hepatitis B virus; LCMV, lymphocytic choriomeningitis virus; NP, nucleoprotein; 2'5' OAS, 2',5'-oligoadenylate synthetase; sALT, serum alanine aminotransferase.


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