A Potential Live Vector, Foamy Virus, Directed Intra-Cellular Expression of Ovine Interferon-.TAU. Exhibited the Resistance to HIV Infection

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Abstract
Interferon-tau (IFN-τ), produced by the embryonic trophectoderm, is a member of type I IFNs required for the establishment of pregnancy in the ruminant ungulates. Although this IFN possesses antiviral activity similar to other type I IFNs, the effectiveness of IFN-τ as an antiviral agent has not been well characterized. To investigate possible antiviral effects of ovine IFN-τ (oIFN-τ), oIFN-τ-GST fusion protein was expressed in E. coli BL21, from which the purified protein isolated possessed anti-viral activity. An apathogenic human foamy virus (hFV) was then used to establish a potential recombinant live vector consisting of oIFN-τ cDNA sense (+) or antisense (-) sequence, oIFN-τ(+)/hFV or oIFN-τ(-)/hFV, respectively. Human hematopoietic and other mammalian cell lines that had been transduced with hFV vector consisting of no oIFN-τ, oIFN-τ(+)/hFV or oIFN-τ(-)/hFV construct were cultured initially for 12 days, and three of cell lines were then maintained for up to 90 days. These cells with oIFN-τ expression directed by hFV exhibited the in vitro cytopathic effect minimally. Transduced cell lines that had been cultured for 90 days were subjected to studies on human immunodeficiency virus type-1 (HIV-1) infection, which was measured with infectivity of viral particles resulted from the GFP inserted T-cell tropic HIV SF2 or macrophage tropic HIV SF162: the number of HIV-1 positive cells was reduced by the hFV driven-intra-cellular oIFN-τ expression. Since oIFN-τ/hFV transduced cells exhibited the resistance to HIV-1 infection and/or replication, oIFN-τ could be considered as one of effective antiviral agents against HIV-1. These results suggest that the hFV genome could be an effective recombinant live vector for the expression of a targeted gene in various cell types.