In an investigation of alternative therapeutic approaches for the treatment of influenza virus infections, the antiviral activities of rimantadine hydrochloride, amantadine hydrochloride, ribavirin, and combinations of these drugs were assessed in vitro. Madin-Darby canine kidney cell monolayers were inoculated with recent isolates of influenza viruses at low multiplicities of infection, and virus titers were determined after 24 h. The combination of rimantadine and ribavirin resulted in an enhanced antiviral effect (a decrease in virus titer of >1.0 logio plaque-forming unit per ml at 24 h relative to the maximal effect of a single drug) against A/USSR/90/77/H1N1, A/Texas/1/77/H3N2, A/New Jersey/76/ HSWlN1, and A/PR/834/HON1 viruses. The degree of inhibition depended on the virus strain used, the drug concentrations, and the virus inoculum. Amantadine and ribavirin showed enhanced activity. Ribavirin in combination with high (50 ,ug/ml), but not low (1.56 to 25 ,ug/ml), concentrations of rimantadine showed an enhanced antiviral effect against B/Hong Kong/72 virus. An assay of MadinDarby canine kidney cell proliferation in the presence of drugs showed that the enhanced inhibitory effect of drug combinations was not due to increased cytotoxicity.The adamantane compounds amantadine hydrochloride (Symmetrel) and rimantadine hydrochloride have well documented prophylactic and therapeutic activities against uncomplicated human influenza A virus infections (6, 17, 27; L.

No abstract

The ability of respiratory syncytial virus (RSV) to induce interferon production by human mononuclear leukocytes was compared with that of influenza viruses. Cell culture fluids were assayed for interferon activity 1, 3 and 7 days after exposure to RSV or to one of two subtypes of influenza A virus (H0N1 and H3N2). RSV induced interferon production inconsistently and in low titers. Varying the multiplicity of infection did not improve the ability of RSV to induce interferon production. In contrast, influenza viruses were effective inducers of interferon production. Seropositivity to the influenza virus strains was not associated with increased interferon titers. Interferon produced after exposure to RSV or to the influenza viruses was resistant to low pH treatment. The data suggest that interferon production may not be a major component of human immunological defense against RSV infection.

No abstract

Human macrophages were exposed to two influenza A viruses representing different subtypes. The donors were likely to have been exposed to one subtype (H3N2) but not to the other (H0N 1). Similar effects upon the macrophages were observed for both subtypes: macrophage enhancement of mitogen-stimulated lymphocyte transformation responses was depressed, and the macrophages produced interferon. In contrast, macrophages exposed to inactivated virus exhibited normal enhancement of lymphocyte transformation response, yet produced interferon, although in lower titers than did macrophages exposed to infectious virus.