Immune activation, viral gene product expression and neurotoxicity in the HIV-1 transgenic rat

ABSTRACT Although inhibition of RNA interference (RNAi) by plant virus proteins has been shown to enhance viral replication and pathogenesis in plants, no viral gene product has as yet been shown to inhibit RNAi in vertebrate cells. Here, we present evidence demonstrating that the highly structured ∼160-nucleotide adenoviral VA1 noncoding RNA can inhibit RNAi at physiological levels of expression. VA1, which is expressed at very high levels in adenovirus-infected cells, potently inhibited RNAi induced by short hairpin RNAs (shRNAs) or human microRNA precursors but did not affect RNAi induced by artificial short interfering RNA duplexes. Inhibition appeared to be due both to inhibition of nuclear export of shRNA or premicro-RNA precursors, competition for the Exportin 5 nuclear export factor, and inhibition of Dicer function by direct binding of Dicer. Together, these data argue that adenovirus infection can result in inhibition of RNAi and identify VA1 RNA as the first viral gene product able to inhibit RNAi in human cells.

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Expression in transgenic plants of a viral gene product that mediates insect transmission of potyviruses.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.86.21.8402 ◽

1989 ◽

Vol 86 (21) ◽

pp. 8402-8406 ◽

Cited By ~ 26

Author(s):

P. H. Berger ◽

A. G. Hunt ◽

L. L. Domier ◽

G. M. Hellmann ◽

Y. Stram ◽

...

Keyword(s):

Transgenic Plants ◽

Gene Product ◽

Viral Gene ◽

Viral Gene Product ◽

Insect Transmission

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Helical polymers of the REV protein of human immunodeficiency virus 1

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012268x ◽

1992 ◽

Vol 50 (1) ◽

pp. 456-457

Author(s):

Manoj Misra ◽

Benes L. Trus ◽

Paul Wingfield ◽

Alasdair C. Steven

Keyword(s):

Rna Virus ◽

Viral Gene Expression ◽

Viral Gene ◽

Helical Polymers ◽

Immunodeficiency Virus ◽

Viral Gene Product ◽

Active Proliferation ◽

Hiv 1 ◽

Rev Protein

The pattern of viral gene expression in cells infected with HIV-1 is orchestrated by several regulatory proteins. One such viral gene product is Rev (regulator of expression of virus), a 13 kDa basic protein that plays a crucial role in determining whether full-length transcripts coding for the major structural proteins of HIV-1 are exported intact from the nucleus into the cytoplasm, so that active proliferation of the virus can ensue. Purified Rov has been shown to polymerize in vitro into long filamentous polymers. Based on this and other observations, it has been hypothesized that Rev functions rather like the nucleocapsid protein of a filamentous RNA virus, and that coating of the transcripts in question by Rev is the mechanism whereby they are protected from splicing. To explore this hypothesis further, we have studied the structure of these Rev polymers in greater detail.

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Use of whole-cell fixation to visualize replicating and maturing simian virus 40: identification of new viral gene product.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.78.10.6081 ◽

1981 ◽

Vol 78 (10) ◽

pp. 6081-6085 ◽

Cited By ~ 36

Author(s):

V. Jackson ◽

R. Chalkley

Keyword(s):

Gene Product ◽

Simian Virus 40 ◽

Simian Virus ◽

Viral Gene ◽

Whole Cell ◽

Viral Gene Product ◽

Cell Fixation

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Faculty Opinions recommendation of An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718231358.793491406 ◽

2014 ◽

Author(s):

Susana Asin ◽

Christiane Rollenhagen

Keyword(s):

Immune Activation ◽

Systemic Immune Activation ◽

Hiv 1

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Integrated analysis of lncRNA, miRNA and mRNA profiles reveals potential lncRNA functions during early HIV infection

Journal of Translational Medicine ◽

10.1186/s12967-021-02802-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Lianwei Ma ◽

Hui Zhang ◽

Yue Zhang ◽

Hailong Li ◽

Minghui An ◽

...

Keyword(s):

Hiv Infection ◽

Immune Activation ◽

Expression Profiles ◽

Critical Role ◽

Differentially Expressed ◽

Integrated Analysis ◽

Target Mrnas ◽

Immunodeficiency Virus ◽

Mirna Sequencing ◽

Hiv 1

Abstract Background Long noncoding RNAs (lncRNAs) can regulate gene expression in a cis-regulatory fashion or as “microRNA sponges”. However, the expression and functions of lncRNAs during early human immunodeficiency virus (HIV) infection (EHI) remain unclear. Methods 3 HAART-naive EHI patients and 3 healthy controls (HCs) were recruited in this study to perform RNA sequencing and microRNA (miRNA) sequencing. The expression profiles of lncRNAs, mRNAs and miRNAs were obtained, and the potential roles of lncRNAs were analysed based on discovering lncRNA cis-regulatory target mRNAs and constructing lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on 175 lncRNA-associated differentially expressed (DE) mRNAs to investigate the potential functions of DE lncRNAs in ceRNA networks. Results A total of 242 lncRNAs, 1240 mRNAs and 21 mature known miRNAs were determined as differentially expressed genes in HAART-naive EHI patients compared to HCs. Among DE lncRNAs, 44 lncRNAs were predicted to overlap with 41 target mRNAs, and 107 lncRNAs might regulate their nearby DE mRNAs. Two DE lncRNAs might regulate their cis-regulatory target mRNAs BTLA and ZAP70, respectively, which were associated with immune activation. In addition, the ceRNA networks comprised 160 DE lncRNAs, 21 DE miRNAs and 175 DE mRNAs. Seventeen DE lncRNAs were predicted to regulate HIF1A and TCF7L2, which are involved in the process of HIV-1 replication. Twenty DE lncRNAs might share miRNA response elements (MREs) with FOS, FOSB and JUN, which are associated with both immune activation and HIV-1 replication. Conclusions This study revealed that lncRNAs might play a critical role in HIV-1 replication and immune activation during EHI. These novel findings are helpful for understanding of the pathogenesis of HIV infection and provide new insights into antiviral therapy.

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