Cell and Virus Sensitivity Studies with Recombinant Human Alpha Interferons

Abstract

The cell sensitivity of recombinant human alpha interferons (rIFN-α)of > 95% purity (A,D and the hybrid A/D) and crude nature (B and F) was studied in human (WISH, HeLa, AG1732), bovine (MDBK, BT), monkey (Vero), mouse (L), rabbit (RK-13), and hamster (BHK-21) cells. Based on an activity of 100% in WISH cells, the other cells responded to rIFN-αA as follows: AG1732 (90%), HeLa (94%), and MDBK and BT cells (170–190%). Rabbit, mouse, and hamster cells had a relative sensitivity of < 1%. rIFN-αB and F were essentially equivalent to rIFN-αA in terms of cell sensitivity, but MDBK and BT cells were about 20 times more sensitive to rIFN-αD than were WISH cells and rIFN-αD was 1/5 to 1/10 as active on L cells as on WISH cells. The activity of the hybrid IFN A/D on bovine, mouse, and human cells was similar. The inhibitory dose₅₀ (U/ml) of rIFN-αA, B, D, and F against virus infections in WISH cells were: vesicular stomatitis virus (1-4), rhinovirus types 1 and 42 (2-18), and herpes simplex virus (HSV) type 2 (45-70). Type 1 HSV, Semliki Forest (SFV) and encephalomyocarditis (EMC) viruses were tested against only rIFN-αA and D where SFV and EMC were the most sensitive to both IFNs (ID₅₀-SFV, 0.2 U/ml, EMC, 1.2 U/ml) while 13 U/ml of rIFN-αA and D inhibited Type 1 HSV. The various rIFN-αs did not exhibit different antiviral spectra in vitro. When tested in mice rIFN-αA did not protect against infections with SFV, EMC, HSV, or influenza viruses. rIFN-αD and A/D protected mice infected with EMC, SFV, or HSV.