scholarly journals Encapsidation of Staufen-2 Enhances Infectivity of HIV-1

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2459
Author(s):  
Kannan Balakrishnan ◽  
Ananda Jaguva Vasudevan ◽  
Krishnaveni Mohareer ◽  
Tom Luedde ◽  
Carsten Münk ◽  
...  
Keyword(s):  
Population Dynamics ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Host Factors ◽  
Viral Population ◽  
Antiviral Protein ◽  
Viral Propagation ◽  
Human Immuno Deficiency Virus ◽  
Nucleocytoplasmic Export ◽  
Hiv 1

Staufen, the RNA-binding family of proteins, affects various steps in the Human Immuno-Deficiency Virus (HIV-1) replication cycle. While our previous study established Staufen-2–HIV-1 Rev interaction and its role in augmenting nucleocytoplasmic export of RRE-containing viral RNA, viral incorporation of Staufen-2 and its effect on viral propagation were unknown. Here, we report that Staufen-2 interacts with HIV-1 Gag and is incorporated into virions and that encapsidated Staufen-2 boosted viral infectivity. Further, Staufen-2 gets co-packaged into virions, possibly by interacting with host factors Staufen-1 or antiviral protein APOBEC3G, which resulted in different outcomes on the infectivity of Staufen-2-encapsidated virions. These observations suggest that encapsidated host factors influence viral population dynamics and infectivity. With the explicit identification of the incorporation of Staufen proteins into HIV-1 and other retroviruses, such as Simian Immunodeficiency Virus (SIV), we propose that packaging of RNA binding proteins, such as Staufen, in budding virions of retroviruses is probably a general phenomenon that can drive or impact the viral population dynamics, infectivity, and evolution.

scholarly journals HIV-1 RNA genome dimerizes on the plasma membrane in the presence of Gag protein

2015 ◽  
Vol 113 (2) ◽  
pp. E201-E208 ◽  
Author(s):  
Jianbo Chen ◽  
Sheikh Abdul Rahman ◽  
Olga A. Nikolaitchik ◽  
David Grunwald ◽  
Luca Sardo ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Viral Replication ◽  
Genetic Information ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Virus Assembly ◽  
Viral Population ◽  
Gag Protein ◽  
Hiv 1 ◽  
Dimerization Process

Retroviruses package a dimeric genome comprising two copies of the viral RNA. Each RNA contains all of the genetic information for viral replication. Packaging a dimeric genome allows the recovery of genetic information from damaged RNA genomes during DNA synthesis and promotes frequent recombination to increase diversity in the viral population. Therefore, the strategy of packaging dimeric RNA affects viral replication and viral evolution. Although its biological importance is appreciated, very little is known about the genome dimerization process. HIV-1 RNA genomes dimerize before packaging into virions, and RNA interacts with the viral structural protein Gag in the cytoplasm. Thus, it is often hypothesized that RNAs dimerize in the cytoplasm and the RNA–Gag complex is transported to the plasma membrane for virus assembly. In this report, we tagged HIV-1 RNAs with fluorescent proteins, via interactions of RNA-binding proteins and motifs in the RNA genomes, and studied their behavior at the plasma membrane by using total internal reflection fluorescence microscopy. We showed that HIV-1 RNAs dimerize not in the cytoplasm but on the plasma membrane. Dynamic interactions occur among HIV-1 RNAs, and stabilization of the RNA dimer requires Gag protein. Dimerization often occurs at an early stage of the virus assembly process. Furthermore, the dimerization process is probably mediated by the interactions of two RNA–Gag complexes, rather than two RNAs. These findings advance the current understanding of HIV-1 assembly and reveal important insights into viral replication mechanisms.

HIV-1 TAR RNA-binding proteins control TAT activation of translation in Xenopus oocytes.

1993 ◽  
Vol 7 (1) ◽  
pp. 214-222 ◽  
Author(s):  
M Braddock ◽  
R Powell ◽  
A D Blanchard ◽  
A J Kingsman ◽  
S M Kingsman
Keyword(s):  
Xenopus Oocytes ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Tar Rna ◽  
Hiv 1

scholarly journals HIV-1 remodels the nuclear pore complex

2011 ◽  
Vol 193 (4) ◽  
pp. 619-631 ◽  
Author(s):  
Anne Monette ◽  
Nelly Panté ◽  
Andrew J. Mouland
Keyword(s):  
Nuclear Export ◽  
Cell Biology ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Immunogold Electron Microscopy ◽  
Nuclear Pore ◽  
Viral Control ◽  
Host Cell Proteins ◽  
Associated Proteins ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) commandeers host cell proteins and machineries for its replication. Our earlier work showed that HIV-1 induced the cytoplasmic retention of nucleocytoplasmic shuttling and ribonucleic acid (RNA)–binding proteins. This retention is dependent on nuclear export of the viral genomic RNA and on changes in the localization and expression level of the nucleoporin (Nup) p62 (Nup62). To further characterize the extent of perturbation induced by HIV-1, we performed proteomics analyses of nuclear envelopes (NEs) isolated from infected T cells. Infection induced extensive changes in the composition of the NE and its associated proteins, including a remarkable decrease in the abundance of Nups. Immunogold electron microscopy revealed the translocation of Nups into the cytoplasm. Nup62 was identified as a component of purified virus, and small interfering RNA depletion studies revealed an important role for this Nup in virus gene expression and infectivity. This detailed analysis highlights the profound effects on NE composition induced by HIV-1 infection, providing further evidence of the magnitude of viral control over the cell biology of its host.

scholarly journals The SARS-CoV-2 RNA interactome

2020 ◽  
Author(s):  
Sungyul Lee ◽  
Young-suk Lee ◽  
Yeon Choi ◽  
Ahyeon Son ◽  
Youngran Park ◽  
...  
Keyword(s):  
Life Cycle ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Virus ◽  
Host Factors ◽  
Therapeutic Interventions ◽  
Host Proteins ◽  
Viral Rnas ◽  
Comprehensive List ◽  
Evolutionarily Conserved

AbstractSARS-CoV-2 is an RNA virus whose success as a pathogen relies on its ability to repurpose host RNA-binding proteins (RBPs) to form its own RNA interactome. Here, we developed and applied a robust ribonucleoprotein capture protocol to uncover the SARS-CoV-2 RNA interactome. We report 109 host factors that directly bind to SARS-CoV-2 RNAs including general antiviral factors such as ZC3HAV1, TRIM25, and PARP12. Applying RNP capture on another coronavirus HCoV-OC43 revealed evolutionarily conserved interactions between viral RNAs and host proteins. Network and transcriptome analyses delineated antiviral RBPs stimulated by JAK-STAT signaling and proviral RBPs responsible for hijacking multiple steps of the mRNA life cycle. By knockdown experiments, we further found that these viral-RNA-interacting RBPs act against or in favor of SARS-CoV-2. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions.

scholarly journals Staufen1 Interacts with Multiple Components of the Ebola Virus Ribonucleoprotein and Enhances Viral RNA Synthesis

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Jingru Fang ◽  
Colette Pietzsch ◽  
Palaniappan Ramanathan ◽  
Rodrigo I. Santos ◽  
Philipp A. Ilinykh ◽  
...  
Keyword(s):  
Rna Synthesis ◽  
Binding Proteins ◽  
Ebola Virus ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Host Factors ◽  
Viral Rna ◽  
Virion Protein ◽  
Public Health Importance

ABSTRACTEbola virus (EBOV) genome and mRNAs contain long, structured regions that could hijack host RNA-binding proteins to facilitate infection. We performed RNA affinity chromatography coupled with mass spectrometry to identify host proteins that bind to EBOV RNAs and identified four high-confidence proviral host factors, including Staufen1 (STAU1), which specifically binds both 3′ and 5′ extracistronic regions of the EBOV genome. We confirmed that EBOV infection rate and production of infectious particles were significantly reduced in STAU1-depleted cells. STAU1 was recruited to sites of EBOV RNA synthesis upon infection and enhanced viral RNA synthesis. Furthermore, STAU1 interacts with EBOV nucleoprotein (NP), virion protein 30 (VP30), and VP35; the latter two bridge the viral polymerase to the NP-coated genome, forming the viral ribonucleoprotein (RNP) complex. Our data indicate that STAU1 plays a critical role in EBOV replication by coordinating interactions between the viral genome and RNA synthesis machinery.IMPORTANCEEbola virus (EBOV) is a negative-strand RNA virus with significant public health importance. Currently, no therapeutics are available for Ebola, which imposes an urgent need for a better understanding of EBOV biology. Here we dissected the virus-host interplay between EBOV and host RNA-binding proteins. We identified novel EBOV host factors, including Staufen1, which interacts with multiple viral factors and is required for efficient viral RNA synthesis.

scholarly journals Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

2020 ◽  
Author(s):  
Mariana Ferrarini ◽  
Avantika Lal ◽  
Rita Rebollo ◽  
Andreas Gruber ◽  
Andrea Guarracino ◽  
...  
Keyword(s):  
Transposable Element ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Meta Analysis ◽  
Host Factors ◽  
Differentially Expressed ◽  
Nonstructural Proteins ◽  
Sequencing Data ◽  
Genome Wide ◽  
Infected Cells

Abstract The novel betacoronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after initially emerging in Wuhan, China. Here we applied a novel, comprehensive bioinformatic strategy to public RNA sequencing and viral genome sequencing data, to better understand how SARS-CoV-2 interacts with human cells. To our knowledge, this is the first meta-analysis to predict host factors that play a specific role in SARS-CoV-2 pathogenesis, distinct from other respiratory viruses. We identified differentially expressed genes, isoforms and transposable element families specifically altered in SARS-CoV-2 infected cells. Well-known immunoregulators including CSF2, IL-32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were overexpressed. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as hnRNPA1, PABPC1 and eIF4b, which may play important roles in the viral life cycle. We also detected four viral sequence variants in the spike, polymerase, and nonstructural proteins that correlate with severity of COVID-19. The host factors we identified likely represent important mechanisms in the disease profile of this pathogen, and could be targeted by prophylactics and/or therapeutics against SARS-CoV-2.

scholarly journals HIV-1 and two avian retroviral 5′ untranslated regions bind orthologous human and chicken RNA binding proteins

Virology ◽  
2015 ◽  
Vol 486 ◽  
pp. 307-320 ◽  
Author(s):  
Matthew Stake ◽  
Deepali Singh ◽  
Gatikrushna Singh ◽  
J. Marcela Hernandez ◽  
Rebecca Kaddis Maldonado ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Untranslated Regions ◽  
Hiv 1

Regulation of HIV-1 Gene Expression by the RNA-Binding Proteins tat and rev

1991 ◽  
pp. 194-218 ◽  
Author(s):  
J. Karn ◽  
C. Dingwall ◽  
M. J. Gait ◽  
S. Heaphy ◽  
M. A. Skinner
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Hiv 1

scholarly journals The mRNA encoding the JUND tumor suppressor detains nuclear RNA-binding proteins to assemble polysomes that are unaffected by mTOR

2020 ◽  
Vol 295 (22) ◽  
pp. 7763-7773 ◽  
Author(s):  
Gatikrushna Singh ◽  
Sarah E. Fritz ◽  
Bradley Seufzer ◽  
Kathleen Boris-Lawrie
Keyword(s):  
Tumor Suppressor ◽  
Rna Binding ◽  
Mutational Analysis ◽  
Rna Binding Proteins ◽  
Mrna Translation ◽  
Cell Types ◽  
Inhibitory Protein ◽  
Ribonucleoprotein Complex ◽  
Nuclear Rna ◽  
Hiv 1

One long-standing knowledge gap is the role of nuclear proteins in mRNA translation. Nuclear RNA helicase A (DHX9/RHA) is necessary for the translation of the mRNAs of JUND (JunD proto-oncogene AP-1 transcription factor subunit) and HIV-1 genes, and nuclear cap-binding protein 1 (NCBP1)/CBP80 is a component of HIV-1 polysomes. The protein kinase mTOR activates canonical messenger ribonucleoproteins by post-translationally down-regulating the eIF4E inhibitory protein 4E-BP1. We posited here that NCBP1 and DHX9/RHA (RHA) support a translation pathway of JUND RNA that is independent of mTOR. We present evidence from reciprocal immunoprecipitation experiments indicating that NCBP1 and RHA both are components of messenger ribonucleoproteins in several cell types. Moreover, tandem affinity and RT–quantitative PCR results revealed that JUND mRNA is a component of a previously unknown ribonucleoprotein complex. Results from the tandem IP indicated that another component of the JUND-containing ribonucleoprotein complex is NCBP3, a recently identified ortholog of NCBP2/CBP20. We also found that NCBP1, NCBP3, and RHA, but not NCBP2, are components of JUND-containing polysomes. Mutational analysis uncovered two dsRNA-binding domains of RHA that are necessary to tether JUND–NCBP1/NCBP3 to polysomes. We also found that JUND translation is unaffected by inhibition of mTOR, unless RHA was down-regulated by siRNA. These findings uncover a noncanonical cap-binding complex consisting of NCBP1/NCBP3 and RHA substitutes for the eukaryotic translation initiation factors 4E and 4G and activates mTOR-independent translation of the mRNA encoding the tumor suppressor JUND.

Sign in / Sign up

Export Citation Format

Share Document