Alterations in HeLa cell metabolism resulting from poliovirus infection

Abstract

Alterations in the cellular metabolism of the S3 strain of HeLa have been determined after simultaneous infection of log-phase suspension cultures with poliovirus. An early effect of virus infection is an inhibition of the net synthesis of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and protein, to the degree that there is no measurable increase in the first 6 hours after infection. This inhibition of synthesis is observed even though the cells are contained in a complete growth medium which permits optimal rates of growth of unin fected cells. Beginning 6 hours after infection there is a sharp loss of cellular material into the medium. Thirty per cent of the cellular RNA is lost between the sixty and ninth hours, and an additional 30–40 % between the ninth and twelfth hours. In contrast, there is no measurable loss of cellular DNA, whereas 20–30 % of the protein is released into the medium between the ninth and twelfth hours. Although there was no measurable net synthesis of RNA, DNA, and protein in polio-infected HeLa cells, there was a progressive increase in the acidsoluble nucleotide pool, beginning at the third hour after infection and continuing until the ninth hour. The rate of that increase significantly exceeds that observed in growing cultures. The possibility is suggested that an early effect of the virus infection is the release of a cellular ribonuclease. Despite the absence of net RNA synthesis, the incorporation of cytidine- 2-C 14 into RNA uracil was essentially the same in infected as in growing cultures, but its incorporation into cytosine was significantly depressed in the infected cultures. The same pattern of incorporation into uracil and cytosine was also observed when net RNA synthesis was prevented by some mechanism other than viral infection, such as the omission of an essential amino acid from the medium. This pattern of cytidine- 2-C 14 incorporation appears to be characteristic of cells under nongrowing conditions. It presumably reflects RNA turnover and is not specifically related to virus infection.