A potential live vector, foamy virus, directed intra-cellular expression of ovine interferon-tau exhibited the resistance to HIV infection

• Published in: Journal of Veterinary Medical Science Vol. 66; no. 2; pp. 115 - 121
• Main Authors: Fujii, Y. (Nagoya City Univ. (Japan)), Murase, Y, Otake, K, Yokota, Y, Omoto, S, Hayashi, H, Okada, H, Okada, N, Kawai, M, Okuyama, H, Imakawa, K
• Format: Journal Article
• Language: English
• Published: Japan JAPANESE SOCIETY OF VETERINARY SCIENCE 01.02.2004
• Subjects: Animals; Antiviral Agents - pharmacology; Blotting, Western; Cell Line; foamy virus; GENETIC VECTORS; Genetic Vectors - metabolism; Green Fluorescent Proteins; HIV; HIV-1 - drug effects; HIV-1 - physiology; Human foamy virus; Human immunodeficiency virus 1; Humans; INTERFERON; Interferon Type I - pharmacology; interferon-tau; live vector; Luminescent Proteins - metabolism; ovine; Pregnancy Proteins - pharmacology; Recombinant Fusion Proteins; RETROVIRIDAE; SHEEP; Spumavirus - genetics; Spumavirus - metabolism; Transduction, Genetic; Virus Replication - drug effects
• ISSN: 0916-7250; 1347-7439
• DOI: 10.1292/jvms.66.115

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.