Anti-HIV-1 Activity of Recombinant and Hybrid Species of Interferon-α

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Abstract
To identify candidate interferons (IFNs) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection and to investigate sequence–function relationships, the antiviral activities of nine species of recombinant IFN-α [IFN-αA, IFN-αB, IFN-αC, IFN-αD, IFN-αJ, [Ser116]IFN-αJ1, IFN-αK, IFN-αJ/C(Fnu4HI), and IFN-αA/D(BglII)] were evaluated against HIV-1. MT-2 cells were exposed to various concentrations of each IFN and were then infected with HIV. Protective effect was determined by cell viability using a tetrazolium dye assay. Activity against vesicular stomatitis virus (VSV) was assessed on MDBK and WISH cells. The 50% inhibitory concentration against HIV was 37 ± 14 pg/ml for IFN-αA, and ranged from 15 ± 3 pg/ml for IFN-αJ/C(Fnu4HI) to >90,000 pg/ml for IFN-αD. In general, relative activity against HIV was similar to relative activity against VSV on WISH cells. IFN-αD was notable for its decreased activity on human cells. The observations suggest that it may be possible to produce IFNs-α with more favorable therapeutic indices than currently available IFNs. Furthermore, the anti-HIV activity of IFNs-α is not determined solely by their linear amino acid sequence.