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Open AccessJournal ArticleDOI

Kinetics of expression of multiply spliced RNA in early human immunodeficiency virus type 1 infection of lymphocytes and monocytes

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TLDR
RNA was analyzed in the early phase of a one-step growth cycle of HIV-1 infection in T-lymphoid and monocytic cell lines by using PCR amplification of in vitro-synthesized viral cDNAs and found that expression of at least small amounts of the singly spliced message could occur before the accumulation of Rev.
Abstract
The genome of human immunodeficiency virus type 1 (HIV-1) encodes at least six proteins involved in regulation as well as the structural proteins Gag, Pol, and Env. The interplay of the various regulators generates early and late transcriptional phases in the HIV-1 life cycle; the earliest RNA is enriched in subgenomic species, and the genomic transcript appears at the later stage of infection. We investigated the nature of the mRNAs expressed in the early stages of infection when the 2 kilobase subgenomic species predominate. RNA was analyzed in the early phase of a one-step growth cycle of HIV-1 infection in T-lymphoid and monocytic cell lines by using PCR amplification of in vitro-synthesized viral cDNAs. In both cell lines, expression of Tat-, Rev-, and Nef-specific messages appeared simultaneously and could be detected within 8-12 hr of infection but in different amounts with a predominance of Nef-specific message. The Env-specific message could be detected as early as the Rev-specific message, indicating that expression of at least small amounts of the singly spliced message could occur before the accumulation of Rev.

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Citations
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Journal ArticleDOI

Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain.

TL;DR: It is demonstrated that Nef acts by inducing CD4 endocytosis, resulting in its degradation in lysosomes, and that CD4 down-regulation is strongly enhanced by the association of Nef with cell membranes through myristoylation.
Journal ArticleDOI

Alternative splicing of human immunodeficiency virus type 1 mRNA modulates viral protein expression, replication, and infectivity.

TL;DR: The redundant RNA splicing signals in the HIV-1 genome and alternatively spliced mRNAs provides a mechanism for regulating the relative proportions of HIV- 1 proteins and, in some cases, viral infectivity.
Journal ArticleDOI

HIV and SIV CTL escape: implications for vaccine design.

TL;DR: These are the important lessons that can be learned from immunodeficiency virus CTL escape that are relevant to vaccine design.
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Association of integrase, matrix, and reverse transcriptase antigens of human immunodeficiency virus type 1 with viral nucleic acids following acute infection

TL;DR: Analysis of viral DNA synthesis and nuclear import of viral nucleoprotein complexes in the presence of a reversible RT inhibitor demonstrated that reverse transcription of viral RNA could be completed entirely in the host cell nucleus.
Journal ArticleDOI

Nef stimulates human immunodeficiency virus type 1 proviral DNA synthesis.

TL;DR: The Nef-mediated stimulation of proviral DNA synthesis is highly conserved and likely plays an important role in vivo, suggesting that Nef acts in producer cells to allow the generation of particles fully competent for completing steps that follow entry, leading to efficient reverse transcription of the HIV-1 genome.
References
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Journal ArticleDOI

Immunodeficiency virus rev trans-activator modulates the expression of the viral regulatory genes.

TL;DR: It is demonstrated that rev not only activates the synthesis of the viral structural proteins, but also modulates the level and quality of HIV-1 regulatory gene expression.
Journal ArticleDOI

Control of retroviral RNA splicing through maintenance of suboptimal processing signals.

TL;DR: It is concluded that splicing is controlled through the maintenance of suboptimal cis-acting signals in the viral RNA that alter the efficiency of recognition by the cellular splicing machinery.
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