Interferon-tau (IFN-τ) was initially identified as an ovine pregnancy protein. Produced by the trophoblast, it is important in preventing degradation of the corpus luteum and has been used as an early marker for ovine pregnancy. As a member of the family of type I interferons, IFN-τ has demonstrated promising antiviral activity against human viral infections in vitro. Additionally, it displays high species cross-reactivity despite its absence in humans. To date, IFN-τ has shown efficacy in reducing replication of human immunodeficiency virus, feline immunodeficiency virus, and human papillomavirus. While IFN-τ shares similar antiviral activity to IFN-α, the current interferon of choice for treatment of viral infections, it lacks the associated toxicity. This may make IFN-τ an attractive alternative to IFN-α for the treatment of viral infections.
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References
1.
AlexenkoAP, EalyAD, BixbyJA, RobertsRM. 2000. A classification for the interferon-tau. J Interferon Cytokine Res, 20,9:817–822.
2.
AlexenkoAP, EalyAD, RobertsRM. 1999. The cross-species antiviral activities of different IFN-tau subtypes on bovine, murine, and human cells: contradictory evidence for therapeutic potential. J Interferon Cytokine Res, 19,12:1335–1341.
3.
AlexenkoAP, LeamanDW, LiJ, RobertsRM. 1997. The antiproliferative and antiviral activities of IFN-tau variants in human cells. J Interferon Cytokine Res, 17,12:769–779.
4.
Asada-KubotaM, UedaT, ShimadaM, TakedaK, SokawaY. 1995. Distribution of immunoreactive 2′,5′-oligoadenylate synthetase in mouse digestive tract. J Interferon Cytokine Res, 15,10:863–867.
5.
BaglioniC, MinksMA, De ClercqE. 1981. Structural requirements of polynucleotides for the activation of (2′–5′) An polymerase and protein kinase. Nucleic Acids Res, 9,19:4939–4950.
6.
BazerFW, SpencerTE, OttTL. 1997. Interferon tau: a novel pregnancy recognition signal. Am J Reprod Immunol, 37,6:412–420.
7.
BocciV. 1999. The oropharyngeal delivery of interferons: where are we and where do we need to go?J Interferon Cytokine Res, 19,8:859–861.
8.
BrodSA. 1999. Autoimmunity is a type I interferon-deficiency syndrome corrected by ingested type I IFN via the GALT system. J Interferon Cytokine Res, 19,8:841–852.
9.
ChardT, CraigPH, MenabaweyM, LeeC. 1986. Alpha interferon in human pregnancy. Br J Obstet Gynaecol, 93,11:1145–1149.
10.
DesaiSY, PatelRC, SenGC, MalhotraP, GhadgeGD, ThimmapayaB. 1995. Activation of interferon-inducible 2′-5′ oligoadenylate synthetase by adenoviral VAI RNA. J Biol Chem, 270,7:3454–3461.
11.
Duc-GoiranP, Robert-GalliotB, LopezJ, ChanyC. 1985. Unusual apparently constitutive interferons and antagonists in human placental blood. Proc Natl Acad Sci USA, 82,15:5010–5014.
12.
EalyAD, LarsonSF, LiuL, AlexenkoAP, WinkelmanGL, KubischHM, BixbyJA, RobertsRM. 2001. Polymorphic forms of expressed bovine interferon-tau genes: relative transcript abundance during early placental development, promoter sequences of genes and biological activity of protein products. Endocrinology, 142,7:2906–2915.
13.
EzashiT, EalyAD, OstrowskiMC, RobertsRM. 1998. Control of interferon-tau gene expression by Ets-2. Proc Natl Acad Sci USA, 95,14:7882–7887.
14.
FujiiY, MuraseY, OtakeK, YokotaY, OmotoS, HayashiH, OkadaH, OkadaN, KawaiM, OkuyamaH, ImakawaK. 2004. A potential live vector, foamy virus, directed intra-cellular expression of ovine interferon-tau exhibited the resistance to HIV infection. J Vet Med Sci, 66,2:115–121.
15.
GendelmanHE, BacaLM, TurpinJ, KalterDC, HansenB, OrensteinJM, DieffenbachCW, FriedmanRM, MeltzerMS. 1990. Regulation of HIV replication in infected monocytes by IFN-alpha. Mechanisms for viral restriction. J Immunol, 145,8:2669–2676.
16.
GodkinJD, BazerFW, MoffattJ, SessionsF, RobertsRM. 1982. Purification and properties of a major, low molecular weight protein released by the trophoblast of sheep blastocysts at day 13-21. J Reprod Fertil, 65,1:141–150.
17.
GodkinJD, BazerFW, RobertsRM. 1984. Ovine trophoblast protein 1, an early secreted blastocyst protein, binds specifically to uterine endometrium and affects protein synthesis. Endocrinology, 114,1:120–130.
18.
GribaudoG, LemboD, CavalloG, LandolfoS, LengyelP. 1991. Interferon action: binding of viral RNA to the 40-kilodalton 2′-5′-oligoadenylate synthetase in interferon-treated HeLa cells infected with encephalomyocarditis virus. J Virol, 65,4:1748–1757.
19.
HasselBA, ZhouA, SotomayorC, MaranA, SilvermanRH. 1993. A dominant negative mutant of 2-5A-dependent RNase suppresses antiproliferative and antiviral effects of interferon. EMBO J, 12,8:3297–3304.
20.
HovanessianAG. 1989. The double stranded RNA-activated protein kinase induced by interferon: dsRNA-PK. J Interferon Res, 9,6:641–647.
21.
IannuzziL, Di MeoGP, GallagherDS, RyanAM, FerraraL, WomackJE. 1993a. Chromosomal localization of omega and trophoblast interferon genes in goat and sheep by fluorescent in situ hybridization. J Hered, 84,4:301–304.
22.
IannuzziL, GallagherDS, RyanAM, Di MeoGP, WomackJE. 1993b. Chromosomal localization of omega and trophoblast interferon genes in cattle and river buffalo by sequential R-banding and fluorescent in situ hybridization. Cytogenet Cell Genet, 62,4:224–227.
23.
ImakawaK, AnthonyRV, KazemiM, MarottiKR, PolitesHG, RobertsRM. 1987. Interferon-like sequence of ovine trophoblast protein secreted by embryonic trophectoderm. Nature, 330,6146:377–379.
24.
ImakawaK, KimMS, Matsuda-MinehataF, IshidaS, IizukaM, SuzukiM, ChangKT, EchternkampSE, ChristensonRK. 2006. Regulation of the ovine interferon-tau gene by a blastocyst-specific transcription factor, Cdx2. Mol Reprod Dev, 73,5:559–567.
25.
JanewayCA, TraversP, WalportM, SholmchickM. 2005. Immunobiology, 6th. New York and London: Garland Science, 823.
26.
JarpeMA, JohnsonHM, BazerFW, OttTL, CurtoEV, KrishnaNR, PontzerCH. 1994. Predicted structural motif of IFN tau. Protein Eng, 7,7:863–867.
27.
JohnsonGA, SpencerTE, HansenTR, AustinKJ, BurghardtRC, BazerFW. 1999. Expression of the interferon tau inducible ubiquitin cross-reactive protein in the ovine uterus. Biol Reprod, 61,1:312–318.
28.
JohnsonJA, HochkeppelHK, GangemiJD. 1999. IFN-tau exhibits potent suppression of human papillomavirus E6/E7 oncoprotein expression. J Interferon Cytokine Res, 19,10:1107–1116.
29.
KatayamaDS, NayarR, ChouDK, CamposJ, CooperJ, Vander VeldeDG, VillareteL, LiuCP, Cornell ManningM. 2005. Solution behavior of a novel type 1 interferon, interferon-tau. J Pharm Sci, 94,12:2703–2715.
30.
KoharaJ, NishikuraY, TajimaM, OnumaM, YokomizoY. 2009. Antiviral effects of bovine IFN-τ and human IFN-α on bovine viral diarrhea virus. Vet Immunol Immunop, 128:331Abstract
31.
KoharaJ, YokomizoY. 2007. In vitro and in vivo effects of recombinant bovine interferon-tau on bovine leukemia virus. J Vet Med Sci, 69,1:15–19.
32.
KrownSE, RealFX, Cunningham-RundlesS, MyskowskiPL, KozinerB, FeinS, MittelmanA, OettgenHF, SafaiB. 1983. Preliminary observations on the effect of recombinant leukocyte A interferon in homosexual men with Kaposi's sarcoma. N Engl J Med, 308,18:1071–1076.
33.
LaneHC, DaveyV, KovacsJA, FeinbergJ, MetcalfJA, HerpinB, WalkerR, DeytonL, DaveyRTJr, FalloonJ. 1990. Interferon-alpha in patients with asymptomatic human immunodeficiency virus (HIV) infection. A randomized, placebo-controlled trial. Ann Intern Med, 112,11:805–811.
34.
LiJ, RobertsRM. 1994. Structure-function relationships in the interferon-tau (IFN-tau). Changes in receptor binding and in antiviral and antiproliferative activities resulting from site-directed mutagenesis performed near the carboxyl terminus. J Biol Chem, 269,40:24826–24833.
35.
MichaelDD, WagnerSK, OcónOM, TalbotNC, RookeJA, EalyAD. 2006. Granulocyte-macrophage colony-stimulating-factor increases interferon-tau protein secretion in bovine trophectoderm cells. Am J Reprod Immunol, 56,1:63–67.
36.
MirandoMA, ShortECJr, GeisertRD, ValletJL, BazerFW. 1991. Stimulation of 2′,5′-oligoadenylate synthetase activity in sheep endometrium during pregnancy, by intrauterine infusion of ovine trophoblast protein-1, and by intramuscular administration of recombinant bovine interferon-alpha I1. J Reprod Fertil, 93,2:599–607.
37.
MujtabaMG, SoosJM, JohnsonHM. 1997. CD4 T suppressor cells mediate interferon tau protection against experimental allergic encephalomyelitis. J Neuroimmunol, 75,1-2:35–42.
38.
MujtabaMG, VillareteL, JohnsonHM. 1999. IFN-tau inhibits IgE production in a murine model of allergy and in an IgE-producing human myeloma cell line. J Allergy Clin Immunol, 104,5:1037–1044.
39.
NakajimaA, SokawaY. 2002. Induction of blood 2′,5′-oligoadenylate synthetase activity in mice by gastric administration of ovine IFN-tau. J Interferon Cytokine Res, 22,3:397–402.
40.
NojimaH, NagaokaK, ChristensonRK, ShiotaK, ImakawaK. 2004. Increase in DNA methylation downregulates conceptus interferon-tau gene expression. Mol Reprod Dev, 67,4:396–405.
41.
OliveiraJF, HenkesLE, AshleyRL, PurcellSH, SmirnovaNP, VeeramachaneniDN, AnthonyRV, HansenTR. 2008. Expression of interferon (IFN)-stimulated genes in extrauterine tissues during early pregnancy in sheep is the consequence of endocrine IFN-tau release from the uterine vein. Endocrinology, 149,3:1252–1259.
42.
OttTL, Van HeekeG, JohnsonHM, BazerFW. 1991. Cloning and expression in Saccharomyces cerevisiae of a synthetic gene for the type-I trophoblast interferon ovine trophoblast protein-1: purification and antiviral activity. J Interferon Res, 11,6:357–364.
43.
OttTL, YinJ, WileyAA, KimHT, Gerami-NainiB, SpencerTE, BartolFF, BurghardtRC, BazerFW. 1998. Effects of the estrous cycle and early pregnancy on uterine expression of Mx protein in sheep (Ovis aries)Biol Reprod, 59,4:784–794.
44.
ParhamP. 2005. The body's defenses against infection. ParhamP. The immune system, 2nd. New York and London: Garland Science, 227–277.
45.
PontzerCH, BazerFW, JohnsonHM. 1991. Antiproliferative activity of a pregnancy recognition hormone, ovine trophoblast protein-1. Cancer Res, 51,19:5304–5307.
46.
PontzerCH, OttTL, BazerFW, JohnsonHM. 1994. Structure/function studies with interferon tau: evidence for multiple active sites. J Interferon Res, 14,3:133–141.
47.
PontzerCH, YamamotoJK, BazerFW, OttTL, JohnsonHM. 1997. Potent anti-feline immunodeficiency virus and anti-human immunodeficiency virus effect of IFN-tau. J Immunol, 158,9:4351–4357.
48.
RadhakrishnanR, WalterLJ, SubramaniamPS, JohnsonHM, WalterMR. 1999. Crystal structure of ovine interferon-tau at 2.1 A resolution. J Mol Biol, 286,1:151–162.
49.
RobertsRM. 2007. Interferon-tau, a Type 1 interferon involved in maternal recognition of pregnancy. Cytokine Growth Factor Rev, 18,5-6:403–408.
50.
RobertsRM, CrossJC, LeamanDW. 1992. Interferons as hormones of pregnancy. Endocr Rev, 13,3:432–452.
51.
RobertsRM, LiuL, GuoQ, LeamanD, BixbyJ. 1998. The evolution of the type I interferons. J Interferon Cytokine Res, 18,10:805–816.
52.
RogezC, MartinM, Dereuddre-BosquetN, MartalJ, DormontD, ClayetteP. 2003. Anti-human immunodeficiency virus activity of tau interferon in human macrophages: involvement of cellular factors and beta-chemokines. J Virol, 77,23:12914–12920.
53.
Rogez-KreuzC, ManéglierB, Dereuddre-BosquetN, DormontD, ClayetteP. 2005. Lack of IFN-gamma production in response to antigenic stimulation in human IFN-tau-treated lymphocytes. J Interferon Cytokine Res, 25,8:444–452.
54.
Rogez-KreuzC, ManéglierB, MartinM, Dereuddre-BosquetN, MartalJ, DormontD, ClayetteP. 2005. Involvement of IL-6 in the anti-human immunodeficiency virus activity of IFN-tau in human macrophages. Int Immunol, 17,8:1047–1057.
55.
RyanAM, GallagherDS, WomackJE. 1992. Syntenic mapping and chromosomal localization of bovine alpha and beta interferon genes. Mamm Genome, 3,10:575–578.
56.
SakuraiT, SakamotoA, MuroiY, BaiH, NagaokaK, TamuraK, TakahashiT, HashizumeK, SakataniM, TakahashiM, GodkinJD, ImakawaK. 2009. Induction of endogenous interferon tau gene transcription by CDX2 and high acetylation in bovine nontrophoblast cells. Biol Reprod, 80,6:1223–1231.
57.
SamuelCE. 1993. The eIF-2 alpha protein kinases, regulators of translation in eukaryotes from yeasts to humans. J Biol Chem, 268,11:7603–7606.
58.
SchmittRA, GeisertRD, ZavyMT, ShortEC, BlairRM. 1993. Uterine cellular changes in 2′,5′-oligoadenylate synthetase during the bovine estrous cycle and early pregnancy. Biol Reprod, 48,3:460–466.
59.
SenGC. 2001. Viruses and interferons. Annu Rev Microbiol, 55:255–281.
60.
SenGC, LengyelP. 1992. The interferon system. A bird's eye view of its biochemistry. J Biol Chem, 267,8:5017–5020.
61.
SendaT, SaitohSI, MitsuiY, LiJ, RobertsRM. 1995. A three-dimensional model of interferon-tau. J Interferon Cytokine Res, 15,12:1053–1060.
62.
ShortsLH, DanczCE, ShuppJW, PontzerCH. 2004. Characterization of N-terminal interferon tau mutants: P26L affords enhanced activity and lack of toxicity. Exp Biol Med (Maywood), 229,2:194–202.
63.
SobelDO, AhvaziB, AmjadF, MitnaulL, PontzerC. 2008. Interferon-tau inhibits the development of diabetes in NOD mice. Autoimmunity, 41,7:543–553.
64.
SoosJM, MujtabaMG, SubramaniamPS, StreitWJ, JohnsonHM. 1997. Oral feeding of interferon tau can prevent the acute and chronic relapsing forms of experimental allergic encephalomyelitis. J Neuroimmunol, 75,1-2:43–50.
65.
SoosJM, SubramaniamPS, HobeikaAC, SchiffenbauerJ, JohnsonHM. 1995. The IFN pregnancy recognition hormone IFN-tau blocks both development and superantigen reactivation of experimental allergic encephalomyelitis without associated toxicity. J Immunol, 155,5:2747–2753.
66.
SubramaniamPS, KhanSA, PontzerCH, JohnsonHM. 1995. Differential recognition of the type I interferon receptor by interferons tau and alpha is responsible for their disparate cyto-toxicities. Proc Natl Acad Sci USA, 92,26:12270–12274.
67.
TennakoonDK, SmithR, StewartMD, SpencerTE, NayakM, WelshCJ. 2001. Ovine IFN-tau modulates the expression of MHC antigens on murine cerebrovascular endothelial cells and inhibits replication of Theiler's virus. J Interferon Cytokine Res, 21,10:785–792.
68.
TuoW, MacMillanH, GünterN, BazerFW, BrownWC. 1999. Upregulation of interleukin-4 and IFN-gamma expression by IFN-tau, a member of the type I IFN family. J Interferon Cytokine Res, 19,2:179–187.
69.
UzeG, BanduMT, EidP, GrütterM, MogensenKE. 1988. Electrostatic interactions in the cellular dynamics of the interferon-receptor complex. Eur J Biochem, 171,3:683–691.
70.
WhaleyAE, MekaCS, HarbisonLA, HuntJS, ImakawaK. 1994. Identification and cellular localization of unique interferon mRNA from human placenta. J Biol Chem, 269,14:10864–10868.
71.
WilliamBRG, SilvermanRH. 1985. The 2-5A system: Molecular and clinical aspects of the interferon-regulated pathway. Proceedings of the Sixth International Symposium of the Research Institute, Hospital for Sick Children. Prog Clin Biol Res, 202:1–478.
72.
YamaguchiH, IkedaY, MorenoJI, KatsumuraM, MiyazawaT, TakahashiE, ImakawaK, SakaiS, ChristensonRK. 1999. Identification of a functional transcriptional factor AP-1 site in the sheep interferon tau gene that mediates a response to PMA in JEG3 cells. Biochem J, 340,Pt 3:767–773.
