scholarly journals Characterization of the Role of Host Cellular Factor Histone Deacetylase 10 during HIV-1 Replication

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 28
Author(s):  
Xiaozhuo Ran ◽  
Zhujun Ao ◽  
Titus Olukitibi ◽  
Xiaojian Yao
Keyword(s):  
Viral Replication ◽  
Histone Deacetylase ◽  
Catalytic Domain ◽  
Inhibitory Factor ◽  
Progeny Virus ◽  
Pcr Analysis ◽  
Transcriptional Level ◽  
Virus Infectivity ◽  
Hiv 1

To date, a series of histone deacetylases have been documented to restrict HIV-1 replication at different steps. In this study, we identified histone deacetylase 10 (HDAC10) as an inhibitory factor against HIV-1 replication. Our results showed that endogenous HDAC10 is downregulated at the transcriptional level during HIV-1 replication. By knocking down HDAC10 in CD4+ T cells with specific shRNAs, we observed that the downregulation of HDAC10 significantly facilitates viral replication. Moreover, RQ-PCR analysis revealed that the downregulation of HDAC10 increased viral integrated DNA. Further, we identified that HDAC10 interacts with the HIV-1 integrase (IN) and that the region of residues from 55 to 165 in the catalytic domain of IN is required for HDAC10 binding. Interestingly, we found that the interaction between HDAC10 and IN specifically decreases the interaction between IN and cellular protein lens epithelium-derived growth factor (LEDGF/p75), which consequently leads to the inhibition of viral integration. In addition, we have investigated the role of HDAC10 in the late stage of viral replication by detecting the infectiousness of progeny virus produced from HDAC10 knockdown cells or HDAC10 overexpressing cells and revealed that the progeny virus infectivity is increased in the HDAC10 downregulated cells, but decreased in the HDAC10 overexpressed cells. Overall, these findings provide evidence that HDAC10 acts as a cellular inhibitory factor at the early and late stages of HIV-1 replication.

scholarly journals Effect of alpha-1 antitrypsin Portland variant (α1-PDX) on HIV-1 replication

2000 ◽  
Vol 352 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Bouchaib BAHBOUHI ◽  
Mourad BENDJENNAT ◽  
Denise GUÉTARD ◽  
Nabil Georges SEIDAH ◽  
Elmostafa BAHRAOUI
Keyword(s):  
Viral Replication ◽  
Potential Role ◽  
Serine Proteinase ◽  
Recombinant Vaccinia Virus ◽  
Jurkat Cells ◽  
Serine Proteinase Inhibitor ◽  
Cdna Insert ◽  
Alpha 1 Antitrypsin ◽  
Hiv 1

The present work investigated the potential role of alpha-1 antitrypsin Portland variant (α1-PDX), a bioengineered serine proteinase inhibitor (serpin), in the interference with the viral replication of HIV-1, induction of syncytia and maturation of envelope glycoprotein gp160 to gp120 and gp41. A Jurkat lymphoid cell line transfected with a plasmid containing the α1-PDX cDNA (J-PDX) and expressing the protein in a stable manner was infected with HIV-1Lai. Controls were Jurkat cells transfected with the same vector pcDNA3 without the cDNA insert (J-pcDNA3). The results showed that viral replication of HIV-1 was significantly inhibited with a delay in replication kinetics in J-PDX cells as compared with J-pcDNA3 cells. In addition, a comparison of the infectious capacity of viruses produced in the presence and absence of α1-PDX revealed that this capacity differed. It was found that α1-PDX exerts its effect by interfering with the formation of syncytia between J-PDX cells infected with gp160 recombinant vaccinia virus, or after infection by HIV-1 and co-culture with uninfected Molt-4 cells. In contrast, when the same experiments were performed with J-pcDNA3 cells, a large number of syncytia was obtained. Analysis of viral proteins by Western blotting and densitometry showed that the inhibition of the cytopathic effect of HIV-1 and viral replication was correlated with the capacity of α1-PDX to interfere with the maturation of gp160 to gp120 and gp41.

scholarly journals Management of HIV-1 associated hepatitis in patients with acquired immunodeficiency syndrome: role of a successful control of viral replication

2011 ◽  
Vol 8 (1) ◽  
pp. 9 ◽  
Author(s):  
Antonella Esposito ◽  
Valentina Conti ◽  
Maria Cagliuso ◽  
Daniele Pastori ◽  
Alessandra Fantauzzi ◽  
...  
Keyword(s):  
Viral Replication ◽  
Acquired Immunodeficiency Syndrome ◽  
Successful Control ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

scholarly journals An insight into the Inhibition of HIV‐1 replication by co‐infecting HHV‐6, HHV‐7 or GVB‐C viruses: Role of Mutually Homologous miRNAs in Downregulation of Viral Replication

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Omar Bagasra ◽  
Mayank Aggarwal ◽  
krishna chaitanya Addanki ◽  
Mohammad Alsayari ◽  
samina Noorali ◽  
...  
Keyword(s):  
Viral Replication ◽  
Insight Into ◽  
Hiv 1

scholarly journals The Examination of Viral Characteristics of HIV-1 CRF07_BC and Its Potential Interaction with Extracellular Galectin-3

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 425
Author(s):  
Chih-Yen Lin ◽  
Wen-Hung Wang ◽  
Szu-Wei Huang ◽  
Chun-Sheng Yeh ◽  
Ruei-Yu Yuan ◽  
...  
Keyword(s):  
Drug Users ◽  
Potential Interaction ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virus Infectivity ◽  
Promoting Effect ◽  
Galectin 3 ◽  
Emerging Virus ◽  
Hiv 1 ◽  
Envelope Gp120

HIV-1 CRF07_BC is a B’ and C subtype recombinant emerging virus and many of its viral characteristics remain unclear. Galectin-3 (Gal3) is a β-galactose binding lectin that has been reported as a pattern recognition receptor (PRR) and is known to mediate adhesion between cells and microbes. This study aims to examine the viral characteristics of HIV-1 CRF07_BC virus and the role of extracellular galectin-3 in HIV-1 CRF07_BC infection. A total of 28 HIV-1+ injecting drug users (IDUs) were recruited and 24 (85.7%) were identified as HIV-1 CRF07_BC. Results indicate that significant higher serum galectin-3 was measured in CRF07_BC infected patients and CRF07_BC infection triggered significant galectin-3 expression (p < 0.01). Viral characteristics demonstrate that CRF07_BC virions display a higher level of envelope gp120 spikes. The virus infectivity assay demonstrated that co-treatment with galectin-3 significantly promoted CRF07_BC attachment and internalization (p < 0.01). A co-immunoprecipitation assay showed that pulldown galectin-3 co-precipitated both CD4 and gp120 proteins. Results from an enzyme-linked immunosorbent assay (ELISA) indicate that the galectin-3 promoting effect occurs through enhancement of the interaction between gp120 and CD4. This study suggests that CRF07_BC was predominant in HIV-1+ IDUs and CRF07_BC utilized extracellular galectin-3 to enhance its infectivity via stabilization of the gp120-CD4 interaction.

scholarly journals Human Immunodeficiency Virus Type 1 cDNA Integration: New Aromatic Hydroxylated Inhibitors and Studies of the Inhibition Mechanism

1998 ◽  
Vol 42 (9) ◽  
pp. 2245-2253 ◽  
Author(s):  
C. M. Farnet ◽  
B. Wang ◽  
M. Hansen ◽  
J. R. Lipford ◽  
L. Zalkow ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Replication ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Catalytic Domain ◽  
Restriction Enzymes ◽  
Inhibition Mechanism ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Integration of the human immunodeficiency virus type 1 (HIV-1) cDNA is a required step for viral replication. Integrase, the virus-encoded enzyme important for integration, has not yet been exploited as a target for clinically useful inhibitors. Here we report on the identification of new polyhydroxylated aromatic inhibitors of integrase including ellagic acid, purpurogallin, 4,8,12-trioxatricornan, and hypericin, the last of which is known to inhibit viral replication. These compounds and others were characterized in assays with subviral preintegration complexes (PICs) isolated from HIV-1-infected cells. Hypericin was found to inhibit PIC assays, while the other compounds tested were inactive. Counterscreening of these and other integrase inhibitors against additional DNA-modifying enzymes revealed that none of the polyhydroxylated aromatic compounds are active against enzymes that do not require metals (methylases, a pox virus topoisomerase). However, all were cross-reactive with metal-requiring enzymes (restriction enzymes, a reverse transcriptase), implicating metal atoms in the inhibitory mechanism. In mechanistic studies, we localized binding of some inhibitors to the catalytic domain of integrase by assaying competition of binding by labeled nucleotides. These findings help elucidate the mechanism of action of the polyhydroxylated aromatic inhibitors and provide practical guidance for further inhibitor development.

scholarly journals SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein

2022 ◽  
Author(s):  
Marius Walter ◽  
Irene P Chen ◽  
Albert Vallejo-Gracia ◽  
Ik-Jung Kim ◽  
Olga Bielska ◽  
...  
Keyword(s):  
Viral Replication ◽  
Catalytic Domain ◽  
Therapeutic Interventions ◽  
Stable Complex ◽  
Structural Protein ◽  
Knock Out ◽  
Protein Interactome ◽  
Lysine Residues ◽  
Dependent Protein

SARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. Nsp14 forms a stable complex with non-structural protein Nsp10 and exhibits exoribonuclease and N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as a putative binding partner of Nsp14. SIRT5 is an NAD-dependent protein deacylase critical for cellular metabolism that removes succinyl and malonyl groups from lysine residues. Here we investigated the nature of this interaction and the role of SIRT5 during SARS-CoV-2 infection. We showed that SIRT5 stably interacts with Nsp14, but not with Nsp10, suggesting that SIRT5 and Nsp10 are parts of separate complexes. We found that SIRT5 catalytic domain is necessary for the interaction with Nsp14, but that Nsp14 does not appear to be directly deacylated by SIRT5. Furthermore, knock-out of SIRT5 or treatment with specific SIRT5 inhibitors reduced SARS-CoV-2 viral levels in cell-culture experiments. SIRT5 knock-out cells expressed higher basal levels of innate immunity markers and mounted a stronger antiviral response. Our results indicate that SIRT5 is a proviral factor necessary for efficient viral replication, which opens novel avenues for therapeutic interventions.

scholarly journals Differential viral RNA methylation contributes to pathogen blocking in Wolbachia-colonized arthropod

2021 ◽  
Author(s):  
Tamanash Bhattacharya ◽  
Liewei Yan ◽  
Hani Zaher ◽  
Irene L.G. Newton ◽  
Richard William Hardy
Keyword(s):  
Virus Replication ◽  
Ectopic Expression ◽  
Viral Rna ◽  
Progeny Virus ◽  
Virus Infectivity ◽  
Virus Inhibition ◽  
Mosquito Cells ◽  
Cytosine Methyltransferase ◽  
Mechanism Operative

Arthropod endosymbiont Wolbachia pipientis is part of a global biocontrol strategy aimed at reducing the spread of mosquito-borne RNA viruses such as alphaviruses. Our prior work examining Wolbachia-mediated pathogen blocking has demonstrated (i) the importance of a host cytosine methyltransferase, DNMT2, in Drosophila, and (ii) viral RNA as a target through which pathogen-blocking is mediated. Here we report on the role of DNMT2 in Wolbachia induced virus inhibition of alphaviruses in Aedes sp.. Mosquito DNMT2 levels were altered in the presence of both viruses and Wolbachia, albeit in opposite directions. Elevated levels of DNMT2 in mosquito salivary glands induced by virus infection were suppressed in Wolbachia colonized animals coincident with a reduction of virus replication, and decreased infectivity of progeny virus. Ectopic expression of DNMT2 in cultured Aedes cells was proviral increasing progeny virus infectivity, and this effect of DNMT2 on virus replication and infectivity was dependent on its methyltransferase activity. Finally, examination of the effects of Wolbachia on modifications of viral RNA by LC-MS showed a decrease in the amount of 5-methylcytosine modification consistent with the down-regulation of DNMT2 in Wolbachia colonized mosquito cells and animals. Collectively, our findings support the conclusion that disruption of 5-methylcytosine modification of viral RNA is an important mechanism operative in pathogen blocking. These data also emphasize the essential role of epitranscriptomic modifications in regulating fundamental processes of virus replication and transmission.

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