scholarly journals Cellular Factors Targeting HIV-1 Transcription and Viral RNA Transcripts

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 495
Author(s):  
Rayhane Nchioua ◽  
Matteo Bosso ◽  
Dorota Kmiec ◽  
Frank Kirchhoff
Keyword(s):  
Defense Mechanisms ◽  
Viral Gene Expression ◽  
Immune Defense ◽  
Viral Rna ◽  
Viral Gene ◽  
Restriction Factors ◽  
Antiviral Protein ◽  
Rna Transcripts ◽  
Cellular Factors ◽  
Hiv 1

Restriction factors are structurally and functionally diverse cellular proteins that constitute a first line of defense against viral pathogens. Exceptions exist, but typically these proteins are upregulated by interferons (IFNs), target viral components, and are rapidly evolving due to the continuous virus–host arms race. Restriction factors may target HIV replication at essentially each step of the retroviral replication cycle, and the suppression of viral transcription and the degradation of viral RNA transcripts are emerging as major innate immune defense mechanisms. Recent data show that some antiviral factors, such as the tripartite motif-containing protein 22 (TRIM22) and the γ-IFN-inducible protein 16 (IFI16), do not target HIV-1 itself but limit the availability of the cellular transcription factor specificity protein 1 (Sp1), which is critical for effective viral gene expression. In addition, several RNA-interacting cellular factors including RNAse L, the NEDD4-binding protein 1 (N4BP1), and the zinc finger antiviral protein (ZAP) have been identified as important immune effectors against HIV-1 that may be involved in the maintenance of the latent viral reservoirs, representing the major obstacle against viral elimination and cure. Here, we review recent findings on specific cellular antiviral factors targeting HIV-1 transcription or viral RNA transcripts and discuss their potential role in viral latency.

scholarly journals Excessive RNA Splicing and Inhibition of HIV-1 Replication Induced by Modified U1 Small Nuclear RNAs

2010 ◽  
Vol 84 (24) ◽  
pp. 12790-12800 ◽  
Author(s):  
Dibyakanti Mandal ◽  
Zehua Feng ◽  
C. Martin Stoltzfus
Keyword(s):  
Rna Splicing ◽  
Virus Production ◽  
Viral Rna ◽  
Splice Sites ◽  
Rna Transcripts ◽  
Cellular Factors ◽  
Novel Strategy ◽  
Definition Of ◽  
T Cell Lines ◽  
Hiv 1

ABSTRACT HIV-1 RNA undergoes a complex splicing process whereby over 40 different mRNA species are produced by alternative splicing. In addition, approximately half of the RNA transcripts remain unspliced and either are used to encode Gag and Gag-Pol proteins or are packaged into virions as genomic RNA. It has previously been shown that HIV-1 splicing is regulated by cis elements that bind to cellular factors. These factors either enhance or repress definition of exons that are flanked by the HIV-1 3′ splice sites. Here we report that expression of modified U1 snRNPs with increased affinity to HIV-1 downstream 5′ splice sites and to sequences within the first tat coding exon act to selectively increase splicing at the upstream 3′ splice sites in cotransfected 293T cells. This results in a decrease of unspliced viral RNA levels and an approximately 10-fold decrease in virus production. In addition, excessive splicing of viral RNA is concomitant with a striking reduction in the relative amounts of Gag processing intermediates and products. We also show that T cell lines expressing modified U1 snRNAs exhibit reduced HIV-1 replication. Our results suggest that induction of excessive HIV-1 RNA splicing may be a novel strategy to inhibit virus replication in human patients.

scholarly journals Structural Insights into APOBEC3-Mediated Lentiviral Restriction

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 587 ◽  
Author(s):  
Krista A. Delviks-Frankenberry ◽  
Belete A. Desimmie ◽  
Vinay K. Pathak
Keyword(s):  
Defense Mechanisms ◽  
Cytidine Deaminase ◽  
Immune Defense ◽  
Restriction Factors ◽  
Intrinsic Immunity ◽  
Viral Pathogens ◽  
Cytidine Deaminases ◽  
Virion Infectivity Factor ◽  
Coordinated Expression ◽  
Hiv 1

Mammals have developed clever adaptive and innate immune defense mechanisms to protect against invading bacterial and viral pathogens. Human innate immunity is continuously evolving to expand the repertoire of restriction factors and one such family of intrinsic restriction factors is the APOBEC3 (A3) family of cytidine deaminases. The coordinated expression of seven members of the A3 family of cytidine deaminases provides intrinsic immunity against numerous foreign infectious agents and protects the host from exogenous retroviruses and endogenous retroelements. Four members of the A3 proteins—A3G, A3F, A3H, and A3D—restrict HIV-1 in the absence of virion infectivity factor (Vif); their incorporation into progeny virions is a prerequisite for cytidine deaminase-dependent and -independent activities that inhibit viral replication in the host target cell. HIV-1 encodes Vif, an accessory protein that antagonizes A3 proteins by targeting them for polyubiquitination and subsequent proteasomal degradation in the virus producing cells. In this review, we summarize our current understanding of the role of human A3 proteins as barriers against HIV-1 infection, how Vif overcomes their antiviral activity, and highlight recent structural and functional insights into A3-mediated restriction of lentiviruses.

scholarly journals Viral Epitranscriptomics

2017 ◽  
Vol 91 (9) ◽  
Author(s):  
Edward M. Kennedy ◽  
David G. Courtney ◽  
Kevin Tsai ◽  
Bryan R. Cullen
Keyword(s):  
Viral Gene Expression ◽  
Model System ◽  
Viral Gene ◽  
Methyl Group ◽  
Rna Transcripts ◽  
Evolutionarily Conserved ◽  
Eukaryotic Mrnas ◽  
To Come ◽  
Over 40 Years ◽  
Hiv 1

ABSTRACT Although it has been known for over 40 years that eukaryotic mRNAs bear internal base modifications, it is only in the last 5 years that the importance of these modifications has begun to come into focus. The most common mRNA modification, the addition of a methyl group to the N 6 position of adenosine (m6A), has been shown to affect splicing, translation, and stability, and m6A is also essential for embryonic development in organisms ranging from plants to mice. While all viral transcripts examined so far have been found to be extensively m6A modified, the role, if any, of m6A in regulating viral gene expression and replication was previously unknown. However, recent data generated using HIV-1 as a model system strongly suggest that sites of m6A addition not only are evolutionarily conserved but also enhance virus replication. It is therefore likely that the field of viral epitranscriptomics, which can be defined as the study of functionally relevant posttranscriptional modifications of viral RNA transcripts that do not change the nucleotide sequence of that RNA, is poised for a major expansion in scientific interest and may well fundamentally change our understanding of how viral replication is regulated.

scholarly journals The [KIL-d] Element Specifically Regulates Viral Gene Expression in Yeast

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 601-609 ◽  
Author(s):  
Zsolt Tallóczy ◽  
Rebecca Mazar ◽  
Denise E Georgopoulos ◽  
Fausto Ramos ◽  
Michael J Leibowitz
Keyword(s):  
Gene Expression ◽  
Phenotypic Expression ◽  
Viral Gene Expression ◽  
Virus Genome ◽  
Viral Rna ◽  
High Rate ◽  
Viral Gene ◽  
Double Stranded Rna ◽  
Yeast Prions ◽  
Killer Virus

Abstract The cytoplasmically inherited [KIL-d] element epigenetically regulates killer virus gene expression in Saccharomyces cerevisiae. [KIL-d] results in variegated defects in expression of the M double-stranded RNA viral segment in haploid cells that are “healed” in diploids. We report that the [KIL-d] element is spontaneously lost with a frequency of 10−4–10−5 and reappears with variegated phenotypic expression with a frequency of ≥10−3. This high rate of loss and higher rate of reappearance is unlike any known nucleic acid replicon but resembles the behavior of yeast prions. However, [KIL-d] is distinct from the known yeast prions in its relative guanidinium hydrochloride incurability and independence of Hsp104 protein for its maintenance. Despite its transmissibility by successive cytoplasmic transfers, multiple cytoplasmic nucleic acids have been proven not to carry the [KIL-d] trait. [KIL-d] epigenetically regulates the expression of the M double-stranded RNA satellite virus genome, but fails to alter the expression of M cDNA. This specificity remained even after a cycle of mating and meiosis. Due to its unique genetic properties and viral RNA specificity, [KIL-d] represents a new type of genetic element that interacts with a viral RNA genome.

scholarly journals Fourth NF-κB site in HIV-1 subtype-C LTR confers functional advantage to viral gene expression

Retrovirology ◽  
2009 ◽  
Vol 6 (S2) ◽  
Author(s):  
Mahesh Bachu ◽  
Rajesh V Murali ◽  
Anil MHKH Babu ◽  
Venkat SRK Yedavalli ◽  
Kuan-Teh Jeang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Subtype C ◽  
Functional Advantage ◽  
Hiv 1

scholarly journals Impact of Tat Genetic Variation on HIV-1 Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-28 ◽  
Author(s):  
Luna Li ◽  
Satinder Dahiya ◽  
Sandhya Kortagere ◽  
Benjamas Aiamkitsumrit ◽  
David Cunningham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Transcriptional Activation ◽  
Viral Gene Expression ◽  
Functional Domains ◽  
Viral Gene ◽  
Molecular Architecture ◽  
Viral Transactivator ◽  
Hiv Drugs ◽  
Hiv 1

The human immunodeficiency virus type 1 (HIV-1) promoter or long-terminal repeat (LTR) regulates viral gene expression by interacting with multiple viral and host factors. The viral transactivator protein Tat plays an important role in transcriptional activation of HIV-1 gene expression. Functional domains of Tat and its interaction with transactivation response element RNA and cellular transcription factors have been examined. Genetic variation withintatof different HIV-1 subtypes has been shown to affect the interaction of the viral transactivator with cellular and/or viral proteins, influencing the overall level of transcriptional activation as well as its action as a neurotoxic protein. Consequently, the genetic variability withintatmay impact the molecular architecture of functional domains of the Tat protein that may impact HIV pathogenesis and disease. Tat as a therapeutic target for anti-HIV drugs has also been discussed.

scholarly journals 8 Implication of the HIV-1 pol gene intragenic enhancer in myeloid-specific viral gene expression

2017 ◽  
Vol 3 ◽  
pp. 8
Author(s):  
R. Verdikt ◽  
L. Colin ◽  
C. Vanhulle ◽  
B. Van Driessche ◽  
A. Kula ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Hiv 1

Differential viral gene expression and its effect on the biological properties of the cell clones of an HIV-1-infected cell line

Virology ◽  
1990 ◽  
Vol 177 (1) ◽  
pp. 380-383 ◽  
Author(s):  
V.S. Kalyanaraman ◽  
V. Rodriguez ◽  
S. Josephs ◽  
R.C. Gallo ◽  
M.G. Sarngadharan
Keyword(s):  
Gene Expression ◽  
Infected Cell ◽  
Cell Line ◽  
Viral Gene Expression ◽  
Biological Properties ◽  
Viral Gene ◽  
Infected Cell Line ◽  
Cell Clones ◽  
Hiv 1

scholarly journals Epitranscriptomic Addition of m5C to HIV-1 Transcripts Regulates Viral Gene Expression

2019 ◽  
Vol 26 (2) ◽  
pp. 217-227.e6 ◽  
Author(s):  
David G. Courtney ◽  
Kevin Tsai ◽  
Hal P. Bogerd ◽  
Edward M. Kennedy ◽  
Brittany A. Law ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Hiv 1
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