On the Role of Ribonucleic Acid in Animal Virus Synthesis

Abstract

Use of metabolic inhibitors provides an effective approach to the study of metabolic requirements of virus reproduction (1). In the area of nucleic acid metabolism it has been shown that inhibition of host deoxyribonucleic acid (DNA) synthesis does not inhibit the multiplication of Newcastle disease (2-4) or poliomyelitis virus (2). Thus, host DNA synthesis is apparently not required for the production of several ribonucleic acid (RNA)-containing viruses; whether preformed DNA is necessary is not known.The present study is concerned with the question whether host RNA plays a role in the reproduction of DNA-containing viruses. This question was explored with the aid of 5,6-dichloro-1-/3-~ribofuranosylbenzimidazole (DRB) 1 and with ribonuclease (RNase).In this communication the inhibitory effects of DRB on adenosine-8-C n uptake into cell RNA, on C14-L-alanine uptake into cell proteins, and on cellular oxygen consumption are described. Blocking of the inhibitory effect of DRB on influenza virus multiplication by adenosine will be reported. In addition, the inhibitory activity of DRB on adenovirns multiplication will be compared with its effect on influenza, poliomyelitis, and vaccinia virus multiplication (5-7).In a second communication (8) results of studies of the effects of RNase on influenza B and vaccinla virus multiplication in the chorioallantoic membrane, and on pock formation by vaccinla and herpes simplex viruses will be described

On the Role of Ribonucleic Acid in Animal Virus Synthesis

“…The demonstration that DRB is inhibitory for vaccinia virus multiplication at the same low concentrations which are inhibitory for multiplication of influenza virus (15), combined with the evidence that DRB inhibits incorporation of precursors into RNA strongly suggested that RNA is, indeed, necessary for vaccinia virus synthesis (1). The results of the present study with RNase provide additional evidence in support of this conclusion.…”

“…Indeed, it appears that host protein synthesis in the chorioallantoic membrane is unusually insensitive to the action of both RNase and DRB, because both of these agents do inhibit amino acid uptake into proteins in other systems (1,(19)(20)(21)(22)(23).…”

“…Culture Medium.--The buffered glucosol medium employed for cultures of chorioallantoic membrane was described in the preceding communication (1). This medium was also used as the diluent for RNase in both in ¢itro and in ~ivo experiments.…”

“…Evidence has been presented in the preceding communication (1) indicating that cellular ribonucleic acid (RNA) plays an important role in the reproduction of deoxyribonucleic acid (DNA)-containing animal viruses. It was shown that 5,6-dichloro-1-/3-D-ribofuranosylbenzimidazole (DRB) 1 inhibits uptake of labeled adenosine into RNA of cells when present in concentrations inhibitory for vaccinia or adenovirus multiplication.…”

SPECTRUM AND CHARACTERISTICS OF THE VIRUS INHIBITORY ACTION OF 2-(Α-Hydroxybenzyl)-Benzimidazole

“…Metabolic Aaivities of Monkey Kidney Cdls.--The procedures used for measurement of oxygen uptake, and for determinations of incorporation of adenosine-8-C 14 into RNA, and of C14-I.-alanine into proteins, were described previously (13). Glucose utilization was measured by the procedure of Park and Johnson (14), and lactic acid production by the procedure of Hullin and Noble (15).…”