Translocation and accumulation of exogeneous hepatitis B virus preS surface proteins in the cell nucleus

Recurrent reports about protease-sensitive sites in the junction of the pre S and S region of the hepatitis B virus large surface protein have raised t he question about a possible biological role of S protein-depleted, indepen dent preS protein fragments in the virus life cycle, In the present study, this question was addressed by exogenous introduction of fluorescence-label ed recombinant preS proteins into permeabilized HepG2 cells. While maltose- binding proteins (MBP) were evenly distributed throughout the cytoplasm, MB P-preS fusion proteins selectively accumulated in the nucleus. Using trunca ted preS proteins, the effective domain for this nuclear accumulation was l ocalized around the preS2 region, The mode of this action differs from conv entional nuclear translocation mechanism in its energy- and mediator-indepe ndency and in that it is not saturated regardless of the increase of preS p rotein concentration. The biological meaning of this phenomenon has to be f urther studied. However, in regard to hepatitis B virus infection, this obs ervation might provide a clue for unveiling the still poorly characterized events after initial internalization of the virus, which might make use of the nuclear translocation effect of the preS2 region to facilitate the infe ction.