INTRACELLULAR RETENTION OF SURFACE PROTEIN BY A HEPATITIS-B VIRUS MUTANT THAT RELEASES VIRION PARTICLES

In the course of chronic infection, hepatitis B virus mutants can some times be found circulating in the serum as the predominant species. On e class of such mutants contains in-frame deletions in the S promoter region. By transfecting hepatoma cells with wild-type or mutant viral genomic DNA, we have shown that one such mutant gives rise to extremel y small amounts of S transcripts, as expected, and therefore expresses very little of the middle and small surface (viral envelope) proteins that are translated from these transcripts, In addition, this mutant gives rise to greater-than-wild-type levels of the preS1 transcripts, which are translated into the large surface protein, Because the large surface protein, unlike the other forms of surface protein, is incomp etent for secretion, cells transfected with the mutant viral DNA conta in large amounts of 20-nm particles within dilated perinuclear vesicle s, Therefore, this and similar S promoter mutants may be one contribut ing factor in the pathogenesis of ground-glass cells, which are hepato cytes containing nonsecretable viral surface proteins within dilated v esicles and are commonly found during chronic hepatitis B, Interesting ly, DNA-containing virion particles are secreted into the medium by ce lls transfected with the mutant DNA, in amounts that are slightly larg er than those secreted from wild-type-transfected cells, apparently be cause the amount of large surface protein is insufficient to block vir ion secretion, This finding mag explain how such mutants can become th e predominant circulating species in the serum, especially if there ar e selection pressures against the mild-type virus.