Potent anti-feline immunodeficiency virus and anti-human immunodeficiency virus effect of IFN-tau.

Potent anti-feline immunodeficiency virus and anti-human immunodeficiency virus effect of IFN-tau.
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DOI:
10.4049/jimmunol.158.9.4351
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发表时间:
1997-05
影响因子:
4.4
通讯作者:
C. Pontzer;J. Yamamoto;F. Bazer;T. Ott;H. Johnson
C. Pontzer;J. Yamamoto;F. Bazer;T. Ott;H. Johnson
中科院分区:
医学2区
文献类型:
--
作者:
C. Pontzer;J. Yamamoto;F. Bazer;T. Ott;H. Johnson

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绵羊IFN-tau是一种新发现的与IFN-α相关的蛋白质,负责绵羊妊娠的母体识别。它已被证明表现出有效的抗病毒和抗增殖活性。为了确定其对猫免疫缺陷病毒(FIV)和HIV的抗病毒活性,在用IFN-tau处理的FIV和HIV感染的猫和人PBL中测定RNA依赖性DNA聚合酶(逆转录酶)的活性。在培养的第6天检测到IFN-tau对逆转录酶活性的显著剂量依赖性抑制,并通过病毒复制的峰值维持。此外,FIV核心蛋白p25的产生被IFN-tau阻断。通过合成肽鉴定,IFN-τ的氨基末端和羧基末端区域似乎参与其抗逆转录病毒活性。IFN-τ和重组人IFN-α 2(rHuIFN-α 2)的抗HIV活性的比较表明,虽然rHuIFN-α 2在10,000 U/ml时对细胞有毒性,但IFN-τ抗逆转录病毒活性与细胞活力或免疫反应性的降低无关。因此,IFN-tau显示出有效的抗FIV和抗HIV活性,而没有与高浓度rHuIFN-a2相关的细胞毒性。
Ovine IFN-tau is a newly described protein related to IFN-alpha that is responsible for maternal recognition of pregnancy in sheep. It has been shown to exhibit potent antiviral and antiproliferative activity. To determine its antiviral activity against feline immunodeficiency virus (FIV) and HIV, the activity of the RNA-dependent DNA polymerase, reverse transcriptase, was assayed in FIV- and HIV-infected feline and human PBL treated with IFN-tau. Significant dose-dependent inhibition of reverse transcriptase activity by IFN-tau was detected by day 6 of culture and was maintained through the peak of virus replication. In addition, production of the FIV core protein, p25, was blocked by IFN-tau. Both the amino- and carboxyl-terminal regions of IFN-tau, as identified by synthetic peptides, appear to be involved in its antiretroviral activity. Comparison of the anti-HIV activities of IFN-tau and recombinant human IFN-alpha2 (rHuIFN-alpha2) indicated that while rHuIFN-alpha2 was toxic to cells at 10,000 U/ml, IFN-tau antiretroviral activity was not associated with a decrease in either cell viability or immunologic reactivity. Thus, IFN-tau displayed potent anti-FIV and anti-HIV activity without the cytotoxicity associated with high concentrations of rHuIFN-alpha2.