Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
tat and rev regulation of human immunodeficiency virus type 1 envelope protein expression in a SV40 late replacement vector.
Diss Abstr Int [B]; 52(7):3438 1992. Unique Identifier : AIDSLINE ICDB/93682501 Lu X; State Univ. of New York at Buffalo
Abstract:
The Human Immunodeficiency Virus type 1 (HIV-1), contains several genes encoding regulatory proteins in addition to the structural protein genes present in all known retroviruses. Two of them, tat and rev, are encoded by the same region of the viral genome. The genes for these proteins contain two overlapping exons which share the same 5' and 3' splice sites, but the proteins are translated in different reading frames. The 14-kD tat protein has been shown to dramatically increase overall viral gene expression primarily at the RNA synthesis level. It acts on a target sequence termed TAR present at the 5' end of all viral mRNAs. In contrast, the 19-kD rev protein has been shown to be a selective transactivator for the viral structural genes. It exerts its function by facilitating transport of the unspliced or singly spliced viral mRNA from nucleus to cytoplasm. A 250-bp fragment termed RRE (rev-responsive element) which maps in the envelope region was shown to be the rev target sequence. In this study, we have shown that expression of the HIV-1 envelope proteins requires the tat/rev 5' splice site in addition to rev in a SV40 expression vector system. First, point mutations in the 5' splice site or deletion of the 5' splice site resulted in virtually total loss of the steady-state level of envelope mRNA even in the presence of the rev protein. Moreover, the envelope expression from a construct lacking the 5' splice site could be restored by inserting a heterologous 5' splice site. The envelope protein expression from a point mutant which could not produce the envelope proteins due to a guanosine to cytidine point mutation at +5 of the tat/rev 5' splice site could be rescued by co-expression of a U1 snRNA containing a compensatory mutation that restored the splice site base-pairing to U1 snRNA. These results clearly demonstrated that U1 snRNA is directly involved in the processing of rev-regulated env mRNA despite the fact the env mRNA remains unspliced. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD91-35117).
Keywords: Gene Expression Regulation, Viral Gene Products, env *Gene Products, rev *Gene Products, tat Genes, Structural, Viral HIV-1/*GENETICS RNA Splicing RNA, Messenger/GENETICS Viral Envelope Proteins/*GENETICS THESIS 930228
M9320868
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Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
