BIOCHEMICAL BASIS FOR ALTERATIONS IN STRUCTURE AND FUNCTION OF HELA CELLS INFECTED WITH NEWCASTLE DISEASE VIRUS

The ability of NDV-infected HeLa cells to synthesize DNA, protein, and RNA was investigated by measuring the incorporation of tritiated precursors into these substances at intervals after infection of cells with a virus/cell multiplicity of 500:1. A significant decrease in incorporation of precursors into DNA and protein was first observed at 3¼ hours after infection. By 4½ hours, an 80 to 90 per cent decrease had occurred, and by 5¼ hours, incorporation of precursors into DNA and protein was almost completely inhibited. Incorporation of precursor into RNA decreased gradually following infection; by the 10th hour, a 40 per cent decrease had occurred. These results, integrated with earlier observations on biological aspects of infection, suggest the following causal relationships among events in NDV-infected cells: (a) The cessation of virus production is probably caused by inhibition of protein or RNA synthesis, and is not due to inhibition of DNA synthesis or to interferon. (b) The production of infective virus does not per se interfere with the ability of an infected cell to divide, nor is inhibition of mitosis caused by either inhibition of DNA synthesis or development of marked degenerative changes in infected cells. Inhibition of mitosis may be the result of inhibition of protein or RNA synthesis, (c) Marked cell damage could have been caused by inhibition of protein, DNA, or RNA synthesis, (d) Interference by NDV with the multiplication of influenza virus was probably due to the inhibitory effects of NDV on cellular biosynthetic activities.