BOVINE PARAINFLUENZA-3 VIRUS SELECTIVELY DEPLETES A CALCIUM-INDEPENDENT, PHOSPHOLIPID-DEPENDENT PROTEIN-KINASE-C AND INHIBITS SUPEROXIDE ANION GENERATION IN BOVINE ALVEOLAR MACROPHAGES

Bovine parainfluenza-3 (PI-3) virus inhibits oxygen-dependent bacteria l killing by phagocytes, a key pulmonary defense, thus predisposing th e host to intrapulmonary bacterial superinfection. PI-3 virus inhibite d opsonized zymosan or PMA-activated superoxide anion (O-2(-)) generat ion in bovine alveolar macrophages. The respiratory virus influenza al so inhibits O-2(-) generation by phagocytes, however, the mechanism(s) of viral inhibition differs from PI-3. PI-3 did not trigger O-2(-) ge neration before inhibition, whereas influenza triggered O-2(-) generat ion before desensitization of ligand-initiated respiratory burst. PI-3 modified the twin signals of calcium and protein kinase C in alveolar macrophages. PI-3 infection increased macrophage membrane permeabilit y to extracellular calcium, but did not inhibit calcium mobilization t riggered by opsonized zymosan. These effects further distinguish bovin e PI-3 from human influenza, which triggers mobilization of cell-assoc iated calcium and inhibits calcium mobilization activated by physiolog ic ligands. Macrophages possessed two classes of PKC activity, a calci um/phosphatidylserine/diglyceride (Ca/PS/DG))-dependent activity and a Ca-independent, PS/DC-dependent histone IIIS phosphorylating activity . PI-3 infection selectively depleted the Ca-independent, PS/DG-depend ent kinase activity but not the classical Ca/PS/DG-dependent activity. inhibition of Ca-independent, PS/DG-dependent kinase activity and inh ibition of O-2(-) generation by PI-3 occurred at a similar viral dose and time frame, suggesting a role for this kinase in activating the re spiratory burst. inhibition of the oxygen-dependent bactericidal funct ion of alveolar macrophages and disturbances in signal transduction ma y contribute to the immunosuppression and bacterial superinfection acc ompanying viral respiratory disease.