EXPRESSION OF THE C-MYC PROTOONCOGENE PRODUCT IN CELLS INFECTED WITH THE HEPATITIS-DELTA VIRUS

The intrahepatic accumulation of the c-myc protooncogene product was o bserved on immunofluorescence in each of six patients with chronic hep atitis delta virus infection who exhibited the hepatitis D antigen in their livers. The c-myc product was stained in the same nuclei that co ntained the hepatitis D antigen. C-myc was not observed in acute hepat itis D or in cases of chronic hepatitis delta virus infection without expression of the hepatitis D antigen. The protooncogene product was d etected in only 1 of 32 viral and nonviral liver disorders unrelated t o hepatitis delta virus. To confirm these observations, we transfected HBsAg-positive (PCL/PRF/5) and HBsAg-negative (HepG2) transformed liv er cell lines with a plasmid containing a hepatitis delta virus cDNA t rimer under the control of the SV40 early enhancer/promoter sequences. Whereas baseline c-myc expression was barely detectable in mock-trans fected PLC/PRF/5 or HepG2 cells, strong c-myc nuclear fluorescence was observed when these same cells were transfected with the hepatitis D antigen expression vector. Similar results were obtained after infecti on of HeLa cells with a recombinant vaccinia virus expressing the hepa titis D antigen. Detection of c-myc mRNA sequences by means of in situ hybridization suggested that the c-myc product accumulation was not d ue to increased amounts of its mRNA. The c-myc protein accumulates sel ectively in the livers of patients with chronic hepatitis delta virus infection and in the same nuclei that contain the hepatitis D antigen. The expression of c-myc in hepatitis D antigen-containing cells does not require the presence of hepatitis B virus infection.