Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;:124.
Multiple RNA splicing sites exist within HIV-1 genomic RNA and these
enable the synthesis of many mRNAs for each of several viral proteins.
We evaluated the biological significance of the alternatively spliced
mRNA species during productive HIV-1 infections of peripheral blood
lymphocytes, human T cell lines, and monocyte-derived macrophage to
determine the potential role of alternative RNA splicing in the
regulation of HIV-1 replication and infection. Firstly, we used a
semi-quantitative PCR assay to determine the relative abundance of the
diverse array of alternatively spliced HIV-1 mRNAs. HIV-1 strains tropic
for monocyte-derived macrophage preferentially utilize splice acceptors
for rev and vpu/env that are not frequently used by T-cell tropic
viruses. Secondly, the effect of altered RNA processing was measured
following mutagenesis of the major 5' splice donor and several cryptic,
constitutive, and competing 3' splice acceptor motifs of HIV-1NL4-3.
Mutations that ablated constitutive splice sites led to the activation
of new cryptic sites; some of these preserved biological function.
Mutations that ablated competing splice acceptor sites caused marked
alterations in the pool of virus-derived mRNAs and, in some instances,
markedly altered virus infectivity and/or the profile of virus proteins.
Redundant RNA splicing signals in the HIV-1 genome and alternatively
spliced mRNAs provide a mechanism for regulating the relative
proportions of HIV-1 proteins and, in some cases, viral infectivity.
*Alternative Splicing Cell Line Human HIV-1/*GENETICS/PATHOGENICITY
Macrophages/VIROLOGY Mutation Polymerase Chain Reaction RNA
Processing, Post-Transcriptional RNA, Messenger/*GENETICS
T-Lymphocytes/VIROLOGY Virus Replication/*GENETICS ABSTRACT