Dissemination of lymphocytic choriomeningitis virus from the gastric mucosa requires G protein-coupled signaling.
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.
Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
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C
Yin
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Djavani
A R
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Schenkel
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Schmidt
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Pauza
M S
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Salvato
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D019204:GTP-Binding Proteins / Q000502:physiology*; D005753:Gastric Mucosa / Q000821:virology*; D017403:In Situ Hybridization; D007275:Injections, Intravenous; D008216:Lymphocytic Choriomeningitis / Q000209:etiology* / Q000503:physiopathology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D037342:Pertussis Toxin; D015398:Signal Transduction; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014779:Virus Replication
D015815:Cell Adhesion Molecules; D017931:DNA Primers; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins