Anti-HIV-1 activity of recombinant and hybrid species of interferon-alpha.
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-alpha [IFN-alpha A, IFN-alpha B, IFN-alpha C, IFN-alpha D, IFN-alpha J, [Ser116]IFN-alpha J1, IFN-alpha K, IFN-alpha J/C(Fnu4HI), and IFN-alpha A/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-alpha A, and ranged from 15 +/- 3 pg/ml for IFN-alpha J/C(Fnu4HI) to > 90,000 pg/ml for IFN-alpha D. In general, relative activity against HIV was similar to relative activity against VSV on WISH cells. IFN-alpha D was notable for its decreased activity on human cells. The observations suggest that it may be possible to produce IFNs-alpha with more favorable therapeutic indices than currently available IFNs. Furthermore, the anti-HIV activity of IFNs-alpha is not determined solely by their linear amino acid sequence.
Sperber
S J
SJ
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903-0019.
Gocke
D J
DJ
Haberzettl
C
C
Kuk
R
R
Schwartz
B
B
Pestka
S
S
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D000595:Amino Acid Sequence; D002470:Cell Survival / Q000187:drug effects; D015497:HIV-1; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014721:Vesicular stomatitis Indiana virus; D014777:Virus Diseases / Q000628:therapy*
D007370:Interferon Type I; D011994:Recombinant Proteins