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 observed on immunofluorescence in each of six patients with chronic hepatitis delta virus infection who exhibited the hepatitis D antigen in their livers. The c-myc product was stained in the same nuclei that contained the hepatitis D antigen. C-myc was not observed in acute hepatitis D or in cases of chronic hepatitis delta virus infection without expression of the hepatitis D antigen. The protooncogene product was detected in only 1 of 32 viral and nonviral liver disorders unrelated to hepatitis delta virus. To confirm these observations, we transfected HBsAg-positive (PCL/PRF/5) and HBsAg-negative (HepG2) transformed liver cell lines with a plasmid containing a hepatitis delta virus cDNA trimer under the control of the SV40 early enhancer/promoter sequences. Whereas baseline c-myc expression was barely detectable in mock-transfected 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 infection of HeLa cells with a recombinant vaccinia virus expressing the hepatitis D antigen. Detection of c-myc mRNA sequences by means of in situ hybridization suggested that the c-myc product accumulation was not due to increased amounts of its mRNA. The c-myc protein accumulates selectively 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.
Tappero
G
G
Clinica Medica Generale, University of Turin Medical School, Orbassano, Italy.
Natoli
G
G
Anfossi
G
G
Rosina
F
F
Negro
F
F
Smedile
A
A
Bonino
F
F
Angeli
A
A
Purcell
R H
RH
Rizzetto
M
M
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000378:metabolism; D002461:Cell Line, Transformed; D005822:Genetic Vectors; D003699:Hepatitis D / Q000378:metabolism* / Q000473:pathology; D003698:Hepatitis Delta Virus / Q000235:genetics; D035923:Hepatitis delta Antigens; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D013194:Staining and Labeling; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism
D000956:Antigens, Viral; D035923:Hepatitis delta Antigens; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc; C442244:hepatitis delta virus large antigen