Biomedical Engineering Reference
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it was closely related to IFN-
. This result was surprising because, in sheep and several other
ruminants, the primary function (and until recently the only known function) of trophoblastin is
to sustain the corpus luteum during the early stages of pregnancy. The 172 amino acid protein is
produced by the trophoblast (an outer layer of cells that surrounds the cells which constitute the
early embryo) for several days immediately preceding implantation. In many ruminants, therefore,
trophoblastin plays an essentially similar role to hCG in humans (Chapter 11).
If amino acid analysis hinted that trophoblastin was in fact an interferon, functional studies
have proven it. These studies show that trophoblastin:
α
•
displays the same antiviral activity as type I interferons;
•
displays anti-proliferative activity against certain tumour cells,
in vitro
at least;
•
binds the type I interferon receptor.
Trophoblastin, therefore, has been named interferon-tau (IFN-τ), and is classifi ed as a type I in-
terferon. There are at least three or four functional IFN-
genes in sheep and cattle. The molecule
displays a molecular mass of 19 kDa and an isoelectric point of 5.5-5.7, in common with other
type I interferons. Interestingly, the molecule can also promote inhibition of reverse transcriptase
activity in cells infected with the HIV virus.
IFN-
τ
is currently generating considerable clinical interest. It induces effects similar to type I
interferon, but it appears to exhibit signifi cantly lower toxicity. Thus, it may prove possible to use
this interferon safely at dosage levels far greater than the maximum dosage levels applied to cur-
rently used type I interferons. This, however, can only be elucidated by future clinical trials.
IFN-
τ
represents an additional member of the interferon (type I) family. This 170 amino acid
glycoprotein exhibits 50-60 per cent amino acid homology to IFN-αs, and appears even more
closely related to IFN-
ω
.
IFN-ω genes have been found in humans, pigs and a range of other mammals, but not in dogs
or rodents. The interferon induces its antiviral, immunoregulatory and other effects by binding the
type I interferon receptor, although the exact physiological relevance of this particular interferon
remains to be elucidated. Recently, a recombinant form of feline IFN-
τ
has been approved within
the EU for veterinary use. Its approved indication is for the reduction of mortality and clinical
symptoms of parvoviral infections in young dogs. The recombinant product is manufactured using
a novel expression system that entails direct inoculation of silkworms with an engineered silk-
worm nuclear polyhedrosis virus housing the feline IFN-
ω
ω
gene, as overviewed in Figure 5.4.
8.4 Conclusion
Interferons represent an important family of biopharmaceutical products. They have a proven
track record in the treatment of selected medical conditions, and their range of clinical applica-
tions continues to grow. It is also likely that many may be used to greater effi cacy in the future by
their application in combination with additional cytokines.
Although it is premature to speculate upon the likely medical applications of IFN-
, the
reduced toxicity exhibited by this molecule will encourage its immediate medical appraisal. The
τ
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