Full text of DOI:10.1089/10799900152434439

JOURNAL OF INTERFERON AND CYTOKINE RESEARCH 21:547–549 (2001)
Mary Ann Liebert, Inc.
Nomenclature of Avian Interferon Proteins
JOHN W. LOWENTHAL,1 PETER STAEHELI,2 URSULA SCHULTZ,3 MARGARET J. SEKELLICK,4
and PHILIP I. MARCUS4
tive protein exhibiting 57% amino acid sequence identity to
HE FIRST AVIAN INTERFERON (IFN) cloned was a type I mol-
ecule from a cDNA library generated from chicken em-
(6)
ChIFN1
genes. Its product was initially designated ChIFN2.
T
Both ChIFN1 and ChIFN2 proteins were acid and heat stable.
The antiviral specific activity of the latter was 20-fold less po-
tent. Direct sequence comparison with mammalian type I IFN
did not allow the designation of these cloned ChIFN as IFN-a
in vitro
bryonic cells that had been aged
to produce large
(1)
amounts of IFN when induced. This chicken interferon
(ChIFN) was indistinguishable from native material in that it
possessed high antiviral activity, was acid and heat stable, in-
ChIFN2
and IFN-b, respectively.The 59 upstreamregion of the
Mx
duced the
gene, was active in a glycosylated or nonglyco-
gene contains a NF-kB consensus motif flanked by a sequence
sylated form, and lacked macrophage-activating factor activ-
ity.(1–3) The first type II ChIFN was cloned from a cDNA
expression library generated from a chicken T cell line and was
shown to be acid and heat labile and capable of inducing nitric
element that could serve as a binding site for transcription fac-
tor IRF-1.(12) These elements are found in mammalian
b
IFN-
IFNA
promoters but are lacking in both mammalian
and
ChIFN1
genes. Furthermore, both mammalian IFN-a and
oxide (NO) and MHC class II antigen expression in chicken
(4,5)
ChIFN1, but not mammalian IFN-b or CHIFN2, are induced
in response to the imiquimod derivative S-28463.
macrophages,
as well as guanylate-binding proteins (GBP)
(12)
Other at-
and IFN regulatory factor-1 (IRF-1) in a chicken fibroblast
line.(5) ChIFN types I and II are antigenicallydistinct.(4–6) Thus,
as in mammalian systems, avian IFN can be assigned to two
types based on biologic, biochemical, and antigenic properties.
tributes of ChIFN1 support its designation as ChIFN-a. Al-
though the overall amino acid identity between mammalian
IFN-a and ChIFN1 is small (24%), there is a highly conserved
region where amino acid sequence identity reaches 80%,(1, Table 1)
a shared alignment for 4 of 6 cysteine residues,(1, Fig. 2) and sec-
ondary structure based on an algorithm for the location of a-
helices that is consistent with three-dimensional models of
mammalian type I IFN.(1, Fig. 6) The high sequence identity, in-
cluding cysteine positions, of the only turkey type I IFN gene
cloned to date and the high degree of antiviral cross-activity of
its protein with chicken cells(7) qualify its designation as Tu-
IFN-a. We favor the designationof ChIFN2 as ChIFN-b based
on its representation as a single gene, its antigenic distinction
from ChIFN1, promoter structure, and a difference in response
to induction by an imiquimod. The type I duck IFN (DuIFN)
is considered a member of the IFN-a family because of its mul-
tiple genes and their inducibility by S-28463,(8,13) while noting
it contains an NF-kB site in the promoter region (U. Schultz
and P. Staeheli, unpublished observation).
Several IFN genes now have been cloned from the
(7–10)
chicken(1–6) as well as from other avian species,
and the
activity of their encoded proteins has been characterized.There
follows a brief description of these characteristics and a stan-
dardized nomenclature for avian IFN based on their genetic,
structural, and functional features. Although avian IFN reveal
low overall levels of amino acid identity to mammalian IFN of
comparable function, conservation of several features, includ-
ing a highly conserved region, along with the analogous bio-
logic and biochemical attributes they share, prompted us to
adopt a similar nomenclature for practical use, recognizing that
(11)
it may not reflect gene phylogeny.
TYPE I
Two serologicallydistinct intronlesstype I ChIFN have been
(6)
identified. Screening of a genomic library with the original
type I ChIFN cDNA(1) identified at least 10
genes that
TYPE II
ChIFN
(6)
differed by only a few base changes from the original. This
The ChIFN cDNA, first cloned from T cells,(4) appears to
encode a typical type II IFN, and like mammalian IFN-g, it ex-
presses antiviral activity, though less on a molar basis than
ChIFN-a; is sensitive to both pH 2 and heat (65°C); upregu-
ChIFN1(2)
family of genes initially was designated
and encoded
biologically active proteins that were at least 99% identical to
each other.(6) A single related gene was identifiedthat was 73%
identical at the nucleotide level and encoded a biologically ac-
1CSIRO Livestock Industries, Geelong, Victoria 3220, Australia.
2Department of Virology, University of Freiburg, D-79104 Freiburg, Germany.
3Department of Internal Medicine II, Molecular Biology, University Hospital Freiburg, 79016, Freiburg, Germany.
4Department of Molecular and Cell Biology, Unit 3044, University of Connecticut, Storrs, CT 06269.
547

548
LOWENTHAL ET AL.
TABLE 1. NOMENCLATURE OF THE AVIAN INTERFERON PROTEINS
Species/family
Protein symbol
Type I Interferon
Original name
Accession no.a
Interferon-alpha family
Chicken(1)
ChIFN-a1ab
ChIFN-a1bc
ChIFN-a1bc
ChIFN-a1cd
TuIFN-a
ChIFN(1)
U07868
X92476
X92477
X92478
U28140
X84764
ChIFN1-1(1,6)
ChIFN1-2(1,6)
ChIFN1-3(6)
TkIFN
Turkey(7)
Duck(8)
DuIFN-ae
DuIFN
Interferon-beta family
Chicken(6)
ChIFN-be
ChIFN2(6)
X92479
Type II Interferon
Interferon-gamma family
Chicken(4)
ChIFN-g
TuIFN-g
PhIFN-g
JqIFN-g
GfIFN-g
DuIFN-g
ChIFN-g
U27465, X99774
AJ000725
Turkey(9)
Ring-necked pheasant(9)
Japanese quail(9)
Guinea fowl(9)
Duck(16)
AJ001289
AJ001678
AJ001263
AF087134, AF100929
aGenBank accession number.
(1)
bOriginal isolate: four identical cDNA clones.
c
(1)
®
One cDNA clone as in original isolate, but Asp
Ser change at position 34. Two identical genomic clones isolated with
this same amino acid change.(6)
d
b
(6)
®
®
Leu at position 27.
One genomic clone as in original isolate, but Leu
Phe at position 19, and Pro
eProvisional assignment (see text).
lates NO production and MHC class II expression in chicken malian and avian IFN and the phylogenetic reconstruction has
macrophages.(4,5,14) ChIFN-g is structurallyand functionallyre- been offered by postulating partial gene conversion events in
IFNA
IFNB
genes
lated to mammalian IFN-g and is encoded by a single gene with gene duplications that gave rise to the
and
introns.(15) Although the amino acid sequence similarity of already established in the last common ancestor of birds and
ChIFN-g to its mammalian counterparts is low (30%–35%), mammals.(21) This scenario has been questioned. However,
(11)
there are highly conserved regions of homology.(4,5,15) Fur- it is recognized that related proteins can diverge on the primary
thermore, based on 3D computer modeling, the structure of structure level yet show similarities at the 3D level. Conse-
ChIFN-g is strikingly similar to that of human and bovine IFN- quently, we argue that the advantage gained by the assignment
g.(16) IFN-g sequences have been derived from other avian of a nomenclature to avian IFN similar to that used in naming
species, including Galliformes(9) and ducks.(17,18) We also note mammalian IFN will not strain the credulity of their evolu-
that type I and type II ChIFN act synergistically,like their mam- tionary relationship but will provide a practical nomenclature
(19)
malian counterparts.
that connotes shared function and mode of action. In this con-
text, we note that the similarity of the genomic organization of
type I receptors reported for birds and mammals(22) adds fur-
ther credence to the use of the proposed nomenclature. Table 1
is modeled after earlier reports on mammalian systems.(23,24)
Designations for gene loci must await information beyond that
reported to date.
EVOLUTIONARY CONSIDERATIONS
Phylogenetic analysis based on amino acid differences be-
tween avian IFN and ancientsubtypesof mammalian type I IFN
IFNA/IFNB
have led to the conclusion that mammalian
genes
originated by duplication of a progenitor after the divergence
of birds, about 310 million years ago.(11,20) This suggests that
DEDICATION
IFNA
IFNB
evolved from a separate and inde-
in birds,
and
pendent gene duplication that gave rise to mammalian type I
This article is dedicated to the memory of William E. Stew-
genes, are not orthologous to counterparts in mammals, and art II,(25) a pioneer in the development of a standard nomen-
hence should be assigned a different nomenclature.(11,20) A pos- clature for interferons and chairman of the first report on in-
Journalof InterferonResearch
sible reconciliation between the biologic, physiochemical, and terferonnomenclature(
1, vi–vii,
structural information that shows relatedness between mam- 1980).

549
NOMENCLATURE OF AVIAN IFN
REFERENCES
15. KAISER, P., WAIN, H.M., and ROTHWELL, L. (1997). Struc-
ture of the chicken interferon-gamma gene, and comparison to
mammalian homologues. Gene 207, 25–32.
16. MICHALSKI, W.P., SHIELL, B.J., O’NEILL, T.E., BEDDOME,
G., and LOWENTHAL, J.W. (1999). Recombinant chicken IFN-
g expressed in Escherichia coli: analysis of C-terminal truncation
and effect on biologic activity. J. Interferon Cytokine Res. 19,
383–392.
17. SCHULTZ, U., and CHISARI, F.V. (1999). Recombinant duck in-
terferon-g: duck homologue of mammalian interferon-g inhibits
duck hepatitis B virus replication in primary duck hepatocytes. J.
Virol. 73, 3162–3168.
1. SEKELLICK, M.J., FERRANDINO, A.F., HOPKINS, D.A., and
MARCUS, P.I. (1994). Chicken interferon gene: cloning, expres-
sion, and analysis. J. Interferon Res. 14, 71–79.
2. SCHULTZ, U., RINDERLE, C., SEKELLICK, M.J., MARCUS,
P.I., and STAEHELI, P. (1995). Recombinant chicken interferon
from Escherichia coli and transfected COS cells is biologically ac-
tive. Eur. J. Biochem. 229, 73–76.
3. SCHULTZ, U., KASPERS, B., RINDERLE, C., SEKELLICK,
M.J., MARCUS, P.I., and STAEHELI, P. (1995). Recombinant
chicken interferon: a potent antiviral agent that lacks intrinsic mac-
rophage activating factor activity. Eur. J. Immunol. 25, 847–851. 18. HUANG, A., SCOUGALL, C.A., LOWENTHAL, J.W., JILBERT,
4. DIGBY, M.R., and LOWENTHAL, J.W. (1995). Cloning and ex-
pression of the chicken interferon-g gene. J. Interferon Cytokine
Res. 15, 939–945.
A.R., and KOTLARSKI, I. (2001). Structural and functional ho-
mology between duck and chicken interferon-gamma. Dev. Comp.
Immunol. 25, 55–68.
5. WEINING, K.C., SCHULTZ, U., MUENSTER, U., KASPERS, 19. SEKELLICK, M.J., LOWENTHAL, J.W., O’NEILL, T.E., and
B., and STAEHELI, P. (1996). Biological properties of recombi-
nant chicken interferon-gamma. Eur. J. Immunol. 26, 2440–2447.
6. SICK, C., SCHULTZ, U., and STAEHELI, P. (1996). A family of
genes coding for two serologically distinct chicken interferons. J.
Biol. Chem. 271, 7635–7639.
7. SURESH, M., KARACA, K., FOSTER, D., and SHARMA, J.M.
(1995). Molecular and functional characteristics of turkey inter-
feron. J. Virol. 69, 8159–8163.
MARCUS, P.I. (1998). Chicken interferons type I and II act syn-
ergistically to enhance an antiviral state and nitric oxide secretion.
J. Interferon Cytokine Res. 18, 407–414.
20. ROBERTS, R.M., LIU, L., GUO, Q., LEAMAN, D., and BIXBY,
J. (1998). The evolution of the type I interferons. J. Interferon Cy-
tokine Res. 18, 805–816.
21. GOGARTEN, J.P., and OLENDZENSKI, L. (1999). Orthologs,
paralogs and genomic comparisons. Curr. Opin. Genet. Dev. 9,
630–636.
8. SCHULTZ, U., KOCK, J., SCHLICHT, H.-J., and STAEHELI, P.
(1995). Recombinant duck interferon: a new reagent for studying 22. REBOUL, J., GARDINER, K., MONNERON, D., UZÉ, G., and
the mode of interferon action against hepatitis B virus. Virology
212, 641–649.
LUTFALLA, G. (1999). Comparative genomic analysis of the in-
terferon/interleukin-10 receptor gene cluster. Genome Res. 9,
242–250.
9. KAISER, P., SONNEMANS, D., and SMITH, L.M. (1998). Avian
IFN-g genes: sequence analysis suggests probable cross-species re-
activity among galliforms. J. Interferon Cytokine Res. 18, 711–719.
10. SICK, C., SCHULTZ, U., MUENSTER, U., MEIER, J.,
KASPERS, B., and STAEHELI, P. (1998). Promoter structures and
differential responses to viral and nonviral chicken type I interferon
genes. J. Biol. Chem. 273, 9749–9754.
11. HUGHES, A.L., and ROBERTS, R.M. (2000). Independent origin
of IFN-g and IFN-b in birds and mammals. J. Interferon Cytokine
Res. 20, 737–739.
23. DIAZ, M.O., BOHLANDER, S., and ALLEN, G. (1996). Nomen-
clature of the human interferon genes. J. Interferon Cytokine Res.
16, 179–180.
24. ALLEN, G., and DIAZ, M.O. (1996). Nomenclature of the human
interferon proteins. J. Interferon Cytokine Res. 16, 181–184.
25. MARCUS, P.I., LIEBERT, M.A., FRIEDMAN, R.M., TOVEY,
M.G., HAVELL, E.A., SONNENFELD, G., DE MAEYER, E., and
GRESSER, I. (2000). Obituary: William E. Stewart II. J. Interferon
Cytokine Res. 20, 839–841.
12. SICK, C., SCHULTZ, U., MUENSTER, U., KASPERS, B., and
STAEHELI, P. (1998). Promoter structures and differential re-
sponses to viral and nonviral inducers of chicken type I interferon.
J. Biol. Chem. 273, 9749–9754.
13. SCHULTZ, U., SUMMERS, J., STAEHELI, P., and CHISARI,
F.V. (1999). Elimination of duck hepatitis B virus RNA-contain-
ing capsids in duck interferon-alpha-treated hepatocytes. J. Virol.
73, 5459–5465.
Address correspondence to:
Dr. Philip Marcus
Department of Molecular and Cell Biology
University of Connecticut
75 North Eagleville Road
Storrs, CT 06269-3044
14. LOWENTHAL, J.W., YORK, J.J., O’NEIL, T.E., RHODES, S.,
PROWSE, S.J., STROM, A.D.G., and DIGBY, M.R. (1997). In
vivo effects of chicken interferon-g during infection with Eimeria.
J. Interferon Cytokine Res. 17, 551–558.
Tel: (860) 486-4254
Fax: (860) 486-5193
pmarcus@uconnvm.uconn.edu
E-mail:

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