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Journal of Virology, November 1998, p. 8613-8619, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Dissemination of Lymphocytic Choriomeningitis Virus from the Gastric Mucosa Requires G Protein-Coupled Signaling

Cheng Yin, Mahmoud Djavani, Alan R. Schenkel, Daniel S. Schmidt, C. David Pauza, and Maria S. Salvato*

Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, Wisconsin 53706

Received 23 April 1998/Accepted 28 July 1998

The gastric mucosa is an important portal of entry for lymphocytic choriomeningitis virus (LCMV) infections. Within hours after intragastric (i.g.) inoculation, virus appears in the gastric epithelia, then in the mesenteric lymph nodes and spleen, and then in the liver and brain. By 72 h i.g.-inoculated virus is widely disseminated and equivalent to intravenous (i.v.) infection (S. K. Rai, B. K. Micales, M. S. Wu, D. S. Cheung, T. D. Pugh, G. E. Lyons, and M. S. Salvato. Am. J. Pathol. 151:633-639, 1997). Pretreatment of mice with a G protein inhibitor, pertussis toxin (PTx), delays LCMV dissemination after i.g., but not after i.v., inoculation. Delayed infection was confirmed by plaque assays, by reverse transcription-PCR, and by in situ hybridization. The differential PTx effect on i.v. and i.g. infections indicates that dissemination from the gastric mucosa requires signals transduced through heterotrimeric G protein complexes. PTx has no direct effect on LCMV replication, but it modulates integrin expression in part by blocking chemokine signals. LCMV infection of macrophages up-regulates CD11a, and PTx treatment counteracts this. PTx may prevent early LCMV dissemination by inhibiting the G protein-coupled chemotactic response of macrophages infected during the initial exposure, thus blocking systemic virus spread.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, 1300 University Ave., Madison, WI 53706. Phone: (608) 262-6058. Fax: (608) 262-9148. E-mail: msalvato{at}facstaff.wisc.edu.

Journal of Virology, November 1998, p. 8613-8619, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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