In the last few years additional members of the interferon family has been discovered. Amino acid sequence analysis of a protein called trophoblastin (which is found in many ruminants) revealed it was closely related to IFN-a. 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:
• 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-t), and is classified as a type I interferon. There are at least three or four functional IFN-t 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-t is currently generating considerable clinical interest. It induces effects similar to type I interferon, but it appears to exhibit significantly lower toxicity. Thus, it may prove possible to use this interferon safely at dosage levels far greater than the maximum dosage levels applied to currently used type I interferons. This, however, can only be elucidated by future clinical trials.
IFN-ro 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-as, and appears even more closely related to IFN-t.
IFN-ro 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-ro 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 silkworm nuclear polyhedrosis virus housing the feline IFN-ro gene, as overviewed in Figure 5.4.
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