Tumorigenic potential of human fibroblasts as a function of ability to express a novel form of influenza A nucleocapsid protein.

Influenza A virus released by infected diploid human fibroblasts contains nearly equal amounts of two electrophoretic forms of the viral nucleocapsid protein NP (NP1 and NP2). Pulse-chase labeling and tryptic fingerprinting of NP1 and NP2 have suggested that NP1 is converted to NP2 late in the lytic cycle as a consequence of a post-translational proteolytic event. Within normal fibroblasts only one cellular form of NP (NP1) is detectable indicating that synthesis of NP2 is associated only with the release of virus from these normal cells. Four neoplastic substrains derived from the normal fibroblast strain exhibit varying degrees of neoplastic character in vitro and tumorigenic potential in athymic mice. This family of human fibroblast strains can be divided into three orders of tumorigenic potential: (i) normal and non-tumorigenic; (ii) neoplastic but rarely tumorigenic; and (iii) neoplastic and always tumorigenic. In contrast to the parental non-tumorigenic cell type which exhibits no cellular NP2, the two classes of neoplastic fibroblasts exhibit NP2 at abundance levels which appear to reflect the two elevated degrees of tumorigenic potential. Thus, assessment of influenza A gene expression may have detected a novel cellular protease which is incrementally elevated along with tumorigenic potential of this human fibroblast family.