Paramyxoviruses activation by host proteases in cultures of normal and cancer cells

Multiplication of paramyxovirus Sendai and Newcastle disease virus (NDV) was studied in cultures of normal and tumor cells. Production of noninfectious virus with uncleaved F0 was observed in canine kidney cell line MDCK (line H) and its derivatives carrying tetracycline-regulated expression of transmembrane protease HAT or TMPRSS2 with trypsin-like cleavage specificity. Under tetracycline induction, a cleavage F0 (65 kD)>F1 (50 kD)+F2(15 kD) and production of infectious virus were observed in these cell cultures. Under tetracycline induction, the additional subunit 38K (m.w. 38 kDa) of the F protein was detected both in infected MDCK-HAT cells and in newly synthesized Sendai virus in addition to F0, F1 and F2, indicating thereby a second HAT-sensitive proteolytic site in the F0 molecule. Highly infectious virus containing cleaved F1+F2 was produced in cultures of cancer cells Caco-2 and H1299. Virus Sendai synthesized in H1299 cells contained 38 K subunit indicating a cleavage of the F0 at a second site by H1299 host cell proteases. Levels of cleaved F1+F2 and infectious virions were higher at the late stage of infection in cancer cells, suggesting thus the induction of virus-activating proteases in Caco-2 and H1299 cells under infection with paramyxoviruses. NDV virus was found to induce more rapid death of cancer cells Caco-2 than Sendai virus. Cooperatively, the obtained data show that cancer cells in distinction to nonmalignant cells can synthesize protease(s) activating infectivity of paramyxoviruses. Thus, they are more vulnerable to paramyxovirus infection than normal cells.

TMPRSS2, paramyxoviruses, proteolytic activation, proteases, HAT, TMPRSS2, apoptosis, cell lysis, viral oncolytics