Cagnon L, Cucchiarini M, Lefebvre J C, Doglio A
Laboratoire de Virologie, Faculté de Médecine, Nice, France.
J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Aug 1;9(4):349-58.
Adenovirus VA1 gene is efficiently transcribed by RNA polymerase III and gives rise to a small highly ordered RNA. To inhibit replication of human immunodeficiency virus (HIV), a chimeric VA1 RNA molecule was designed that contained a short antisense RNA sequence complementary to a conserved region of the HIV-1 rev encoding mRNA (28 nucleotides). This sequence, which was inserted into a projecting loop of the VA1 RNA central domain, was mainly single stranded and available for binding with its complementary sequence. The chimeric VA1 antisense was abundantly expressed in human cells constituting 3% of mRNA and promoted strong and specific inhibition of HIV-1 gene replication. The stable expression of antisense RNA in human T cells (CEM) protected these cells from HIV-1 multiplication for at least 3 months. No side effects were detected because of the lack of antisense effect upon replication of the closely related HIV-2. The VA1 gene may provide a suitably compact gene cassette for the intracellular expression of short antisense RNA directed against HIV.
腺病毒VA1基因由RNA聚合酶III高效转录，并产生一种高度有序的小RNA。为了抑制人类免疫缺陷病毒（HIV）的复制，设计了一种嵌合VA1 RNA分子，其包含与HIV-1 rev编码mRNA的保守区域互补的短反义RNA序列（28个核苷酸）。该序列插入到VA1 RNA中央结构域的突出环中，主要为单链，可用于与其互补序列结合。嵌合VA1反义RNA在人类细胞中大量表达，占mRNA的3%，并促进对HIV-1基因复制的强烈而特异性的抑制。反义RNA在人T细胞（CEM）中的稳定表达使这些细胞免受HIV-1增殖影响至少3个月。由于对密切相关的HIV-2复制缺乏反义效应，未检测到副作用。VA1基因可能为针对HIV的短反义RNA的细胞内表达提供一个合适的紧凑型基因盒。
