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 cho riomeningitis virus (LCMV) infections. Within hours after intragastric (i,g,) inoculation, virus appears in the gastric epithelia, then in t he mesenteric lymph nodes and spleen, and then in the liver and brain. By 72 h i,g,-inoculated virus is widely disseminated and equivalent t o intravenous (i,v,) infection (S, K, Rai, B, K, Micales, M, S, Wu, D, S, Cheung, T, D, Pugh, G, E. Lyons, and hi, 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 ass ays, by reverse transcription-PCR, and by in situ hybridization, The d ifferential PTx effect on i,v, and i,g, infections indicates that diss emination from the gastric mucosa requires signals transduced through heterotrimeric G protein complexes. PTx has no direct effect on LCMV r eplication, but it modulates integrin expression in part by blocking c hemokine signals. LCR IV infection of macrophages up-regulates CD11a, and PTx treatment counteracts this, PTx may prevent early LCMV dissemi nation by inhibiting the G protein-coupled chemotactic response of mac rophages infected during the initial exposure, thus blocking systemic virus spread.