title: Lead aggravates viral disease and represses the antiviral activity of interferon inducers.
abstract: Lead acetate was administered continuously in the drinking water to CD-1 male mice beginning at 4 weeks of age. An LD(10-20) of the lytic viruses or 300 plaque-forming units of RLV was inoculated intrapertioneally at 6 weeks of age. Lead increased the response of the mice to all classes of viruses against which it was tested: an RNA picornavirus-encephalomyocarditis (EMCV), a DNA herpesvirus-pseudoribies, an RNA leukemia-virus-Rauscher leukemia (RLV), an RNA arbovirus B-St. Louis encephalitis, and an RNA arbovirus A-western encephalitis. Most studies were performed between lead and EMCV. Increases in EMCV mortality in lead treated mice over controls ranged from 2x at a lead level of 0.004M to 7x (100% mortality) at a 0.1M lead level. Splenomegaly with spleens 800 to 1100 mg in weight containing high titers of RLV occurred in lead (0.03M)-treated mice 3 and 6 weeks after RLV inoculation; spleens or RLV controls were normal in weight (200 mg) and were free of virus. Lead did not reduce the protective effect of mouse interferon (IF) against the lethal action of EMCV, but it did repress the EMCV antiviral effect of poly I/poly C (PIC) and of Newcastle disease virus (NDV) against EMCV mortality. These data indicate several new facts concerning adverse effects lead may have on an animal: (1) lead aggravates viral disease, most likely in part, through reduced IF synthesis; (2) lead represses the anti-EMCV protective effects of both PIC and of NDV, which, in other reports, were shown to induce IF in radioresistant macrophages (PIC) or in radiosensitive lymphocytes (NDV); (3) lead may then be said to repress IF induction in two kinds of cells; (4) however, lead does not inhibit IF action.
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000037:antagonists & inhibitors; D004665:Encephalitis Virus, St. Louis / Q000187:drug effects; D004667:Encephalitis Virus, Western Equine / Q000187:drug effects; D004668:Encephalitis Viruses / Q000187:drug effects; D004686:Encephalomyocarditis virus / Q000187:drug effects*; D006564:Herpesviridae / Q000187:drug effects; D007372:Interferons / Q000096:biosynthesis; D007854:Lead / Q000494:pharmacology / Q000633:toxicity*; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D009522:Newcastle disease virus / Q000187:drug effects*; D011070:Poly I-C / Q000037:antagonists & inhibitors*; D011925:Rauscher Virus / Q000187:drug effects; D014762:Viral Interference / Q000187:drug effects; D014777:Virus Diseases
chemical_list: D000998:Antiviral Agents; D007854:Lead; D007372:Interferons; D011070:Poly I-C