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

Abstract

Influenza A virus released by infected diploid human fibroblasts contains nearly equal amounts of two electrophoretic forms of the viral nucleocapsid protein NP (NP ₁ and NP ₂ ). Pulse-chase labeling and tryptic fingerprinting of NP ₁ and NP ₂ have suggested that NP ₁ is converted to NP ₂ late in the lytic cycle as a consequence of a post-translational proteolytic event. Within normal fibroblasts only one cellular form of NP (NP ₁ ) is detectable indicating that synthesis of NP ₂ 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 NP ₂ the two classes of neoplastic fibroblasts exhibit NP ₂ 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.