ANTISENSE RNA-MEDIATED INHIBITION OF BOVINE LEUKEMIA VIRUS REPLICATION IN TRANSGENIC RABBITS

Kozireva S., Tomsone V.

It has been demonstrated that the antisense (as) gene targeted at the LTR R-U5 region of BLV genome confers enhanced resistance to BLV infection in primary transgenic rabbits and their F1 offspring, compared to wild type rabbits. In the present work we investigated the heredity of as-gene transgenicity in the offspring of F2–F6 generations of rabbits as well as the duration of both the asRNA expression in transgenic offspring and the inhibitory effect on BLV replication. The as-gene was present in offspring of all five sequential generations, in accordance with Mendel’s distribution. While BLV proviral DNA was present in both T and B cells of all infected non-transgenic animals, in transgenic BLV-infected rabbits, it was found only in T cells, indicating that the latter animals were partially protected against BLV infection. Throughout all the period of constant asRNA expression in the infected transgenic rabbits the expression of BLV LTR was markedly lower and pX sequence expression was not found. When the asRNA was no longer expressed, expression of the pX BLV was observed and the level of BLV LTR expression in infected transgenic rabbit became equal to that in infected non-transgenic animals. Our results indicate that, even if the level of expression of asRNA is not sufficient to completely block BLV reproduction, it is sufficient to inhibit the viral replication cycle and the inhibition occurs before and after proviral DNA is established.

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