EXPRESSION OF NATURALLY-OCCURRING ANTISENSE RNA INHIBITS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 HETEROLOGOUS STRAIN REPLICATION

Recently, the presence of human immunodeficiency virus type 1 (HIV-1) RNA transcripts with negative-strand polarity has been shown in tissue culture models of acute and persistently infected cells. One of these transcripts encodes a 189 amino acid open reading frame. This highly conserved antisense sequence is complementary to the structured Rev-re sponsive element and extends through the cleavage site of the Env prot ein. We tested the ability of this antisense RNA to modulate HIV-1 rep lication and the mRNA profile when expressed stably or transiently in several cell types. Different cell lines and PBLs were transduced by r etroviral vectors producing antisense RNA and were then challenged by HIV infection. We have shown that the endogenously expressed antisense RNA containing the natural open reading frame inhibits HIV-1(IIIB) an d HIV-1(NDK) replication in these cells. The level of inhibition varie d according to the cells, but was significant in all cases. The produc tion of HIV-1 (BRU, IIIB, NDK) mRNAs was also significantly decreased. HIV-2 replication was not inhibited by expression of the antisense RN A. Our results also suggest that this inhibitory effect is due to the antisense RNA and not to the protein which is encoded by this sequence .