scholarly journals The human immunodeficiency virus type 1 Rev protein: ménage à trois during the early phase of the lentiviral replication cycle

2010 ◽  
Vol 91 (8) ◽  
pp. 1893-1897 ◽  
Author(s):  
Bastian Grewe ◽  
Klaus Überla
Keyword(s):  
Early Phase ◽  
Late Phase ◽  
Replication Cycle ◽  
Main Function ◽  
Human Immunodeficiency Viruses ◽  
Cellular Cofactor ◽  
Cell Genome ◽  
Virus Replication Cycle ◽  
Hiv 1 ◽  
Rev Protein

The Rev protein of human immunodeficiency viruses (HIV) has long been recognized to be essential for the late phase of the virus replication cycle, due to its strong enhancement of expression of viral structural proteins. Surprisingly, a number of recent papers have demonstrated that Rev can also interfere with integration of the reverse-transcribed cDNA into the host-cell genome. This seems to be due to Rev's binding to integrase and LEDGF/p75, an important cellular cofactor of HIV-1 integration. As Rev is presumably expressed at sufficiently high levels only after the encoding genome has already integrated, the main function of Rev during the early phase might be to reduce genotoxicity due to excessive integration events after superinfection of the same cell by subsequent viruses. Other potential consequences for HIV-1 replication and evolution after co-infection of the same cell with two viruses are discussed.

Viral gene products and replication of the human immunodeficiency type 1 virus

1994 ◽  
Vol 266 (5) ◽  
pp. C1135-C1156 ◽  
Author(s):  
C. D. Morrow ◽  
J. Park ◽  
J. K. Wakefield
Keyword(s):  
Host Cell ◽  
Early Phase ◽  
Viral Genome ◽  
Social Issues ◽  
Late Phase ◽  
Viral Proteins ◽  
Cell Surface Receptor ◽  
Rna Genome ◽  
Cell Chromosome ◽  
Hiv 1

The acquired immunodeficiency syndrome (AIDS) epidemic represents a modern-day plague that has not only resulted in a tragic loss of people from a wide spectrum of society but has reshaped our viewpoints regarding health care, the treatment of infectious diseases, and social issues regarding sexual behavior. There is little doubt now that the cause of the disease AIDS is a virus known as the human immunodeficiency virus (HIV). The HIV virus is a member of a large family of viruses termed retroviruses, which have as a hallmark the capacity to convert their RNA genome into a DNA form that then undergoes a process of integration into the host cell chromosome, followed by the expression of the viral genome and translation of viral proteins in the infected cell. This review describes the organization of the HIV-1 viral genome, the expression of viral proteins, as well as the functions of the accessory viral proteins in HIV replication. The replication of the viral genome is divided into two phases, the early phase and the late phase. The early phase consists of the interaction of the virus with the cell surface receptor (CD4 molecule in most cases), the uncoating and conversion of the viral RNA genome into a DNA form, and the integration into the host cell chromosome. The late phase consists of the expression of the viral proteins from the integrated viral genome, the translation of viral proteins, and the assembly and release of the virus. Points in the HIV-1 life cycle that are targets for therapeutic intervention are also discussed.

scholarly journals Multiple Roles of HIV-1 Capsid during the Virus Replication Cycle

2019 ◽  
Vol 34 (2) ◽  
pp. 119-134 ◽  
Author(s):  
Mariia Novikova ◽  
Yulan Zhang ◽  
Eric O. Freed ◽  
Ke Peng
Keyword(s):  
Virus Replication ◽  
Multiple Roles ◽  
Replication Cycle ◽  
Virus Replication Cycle ◽  
Hiv 1

scholarly journals Human Cytomegalovirus TRS1 Protein Is Required for Efficient Assembly of DNA-Containing Capsids

2004 ◽  
Vol 78 (19) ◽  
pp. 10221-10229 ◽  
Author(s):  
Joan E. Adamo ◽  
Jörg Schröer ◽  
Thomas Shenk
Keyword(s):  
Virus Replication ◽  
Human Cytomegalovirus ◽  
Dna Cleavage ◽  
Late Phase ◽  
Mutant Virus ◽  
Replication Cycle ◽  
Tegument Protein ◽  
Deficient Mutant ◽  
Infected Cells ◽  
Virus Replication Cycle

ABSTRACT The human cytomegalovirus tegument protein, pTRS1, appears to function at several discrete stages of the virus replication cycle. We previously demonstrated that pTRS1 acts during the late phase of infection to facilitate the production of infectious virions. We now have more precisely identified the late pTRS1 function by further study of a mutant virus lacking the TRS1 region, ADsubTRS1. We observed a significant reduction in the production of capsids, especially DNA-containing C-capsids, in mutant virus-infected cells. ADsubTRS1 exhibited normal cleavage of DNA concatemers, so the defect in C-capsid production must occur after DNA cleavage and before DNA is stably inserted into a capsid. Further, the normal virus-induced morphological reorganization of the nucleus did not occur after infection with the pTRS1-deficient mutant.

scholarly journals Nuclear RNA Export and Packaging Functions of HIV-1 Rev Revisited

2010 ◽  
Vol 84 (13) ◽  
pp. 6598-6604 ◽  
Author(s):  
Maik Blissenbach ◽  
Bastian Grewe ◽  
Bianca Hoffmann ◽  
Sabine Brandt ◽  
Klaus Überla
Keyword(s):  
Nuclear Export ◽  
General Notion ◽  
Main Function ◽  
Hiv Replication ◽  
Major Function ◽  
Nuclear Rna ◽  
Rna Export ◽  
Nuclear Rna Export ◽  
Hiv 1 ◽  
Rev Protein

ABSTRACT Although the viral Rev protein is necessary for HIV replication, its main function in the viral replication cycle has been controversial. Reinvestigating the effect of Rev on the HIV-1 RNA distribution in various cell lines and primary cells revealed that Rev enhanced cytoplasmic levels of the unspliced HIV-1 RNA, mostly 3- to 12-fold, while encapsidation of the RNA and viral infectivity could be stimulated >1,000-fold. Although this clearly questions the general notion that the nuclear export of viral RNAs is the major function of Rev, mechanistically encapsidation seems to be linked to nuclear export, since the tethering of the nuclear export factor TAP to the HIV-1 RNA also enhanced encapsidation. Interference with the formation of an inhibitory ribonucleoprotein complex in the nucleus could lead to enhanced accessibility of the cytoplasmic HIV-1 RNA for translation and encapsidation. This might explain why Rev and tethered TAP exert the same pattern of pleiotropic effects.

scholarly journals A new role of the HIV-1 nucleocapsid in the spatiotemporal control of the reverse transcription throughout the virus replication cycle

Retrovirology ◽  
2009 ◽  
Vol 6 (S2) ◽  
Author(s):  
Bing Yu ◽  
Laurent Houzet ◽  
Ludovic Didierlaurent ◽  
Célia Chamontin ◽  
Zakia Morichaud ◽  
...  
Keyword(s):  
Virus Replication ◽  
Reverse Transcription ◽  
Replication Cycle ◽  
Virus Replication Cycle ◽  
Spatiotemporal Control ◽  
Hiv 1

scholarly journals Cellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction

2021 ◽  
Vol 9 (11) ◽  
pp. 2207
Author(s):  
Tamás Richárd Linkner ◽  
Viktor Ambrus ◽  
Balázs Kunkli ◽  
Zsófia Ilona Szojka ◽  
Gergő Kalló ◽  
...  
Keyword(s):  
Early Phase ◽  
Rna Binding ◽  
Late Phase ◽  
Lentiviral Vectors ◽  
Cellular Protein ◽  
Complex Life Cycle ◽  
Label Free ◽  
Time Points ◽  
Transcriptomic Changes ◽  
Hiv 1

Lentivirus-based vectors derived from human immunodeficiency viruses type 1 and 2 (HIV-1 and 2) are widely used tools in research and may also be utilized in clinical settings. Like their parental virions, they are known to depend on the cellular machinery for successful gene delivery and integration. While most of the studies on cellular proteomic and transcriptomic changes have focused on the late phase of the transduction, studies of those changes in early time-points, especially in the case of HIV-2 based vectors, are widely lacking. Using second generation HIV-1 and 2 vesicular stomatitis virus G protein (VSV-G) pseudotyped lentiviral vectors, we transduced HEK-293T human embryonic kidney cells and carried out transcriptomic profiling at 0 and 2 h time points, with accompanying proteomic analysis at 2 h following transduction. Significant variations were observed in gene expression profile between HIV-1 and HIV-2 transduced samples. Thrombospondin 1 (THBS1), collagens (COL1A2, COL3A1), and eukaryotic translation factors (EIF3CL) in addition to various genes coding for long non-coding RNA (lncRNA) were significantly upregulated 2 h after HIV-2 transduction compared to HIV-1. Label-free quantification mass spectrometry (MS) indicated that seven proteins involved in RNA binding, mRNA transport, and chaperoning were significantly downregulated. The identification of cellular protein targets of lentiviral vectors and their effect on the cellular transcriptome will undoubtedly shed more light on their complex life cycle and may be utilized against infection by their parental lentiviruses. Furthermore, characterizing the early phase of HIV-2 infection may aid in the understanding of its pathomechanism and long incubation period.

Improved Stage Categorization of PTZ-Induced Kindling and Late Enhanced Neurogenesis in PTZ Kindled Mice

2019 ◽  
Vol 8 ◽  
pp. 1511
Author(s):  
Marzieh Shahpari ◽  
Hadi Aligholi ◽  
Mohammad Reza Namavar ◽  
Farzaneh Vafaee ◽  
Masoumeh Emamghoreishi
Keyword(s):  
Subventricular Zone ◽  
Early Phase ◽  
Hind Limb ◽  
Late Phase ◽  
The Other ◽  
Myoclonic Jerk ◽  
Ptz Kindling ◽  
First Occurrence ◽  
Tonic Extension ◽  
Behavioral Index

Background: There is no universally accepted behavioral scoring to define the early development of phenothiazine (PTZ) kindling. Therefore, studies investigating alterations of neurogenesis in the PTZ model were mainly focused on full kindled animals rather than early stages of kindling. This study aimed to determine an appropriate behavioral index for categorizing stages of PTZ kindling progress and to evaluate neurogenesis during PTZ kindling. Materials and Methods: Twenty-four mice were intraperitoneally injected with a sub convulsive dose of PTZ (40mg/kg) every other day until they became full kindled. The first occurrence of different seizure behaviors and their durations were recorded during kindling development, and the different stages of kindling were categorized. Neurogenesis was evaluated in the lateral subventricular zone (SVZ) at each stage of kindling by immunofluorescence staining. Results: First occurrence of restlessness, motionless staring, hind limb tonic extension, Straub’s tail, myoclonic jerk, and tonic-clonic were sequentially observed in more than 80% of animals with increasing PTZ injections. The duration of the myoclonic jerk was significantly longer than the other seizure behaviors. The significantly higher percentage of BrdU-positive cells was found in SVZ of mice showing tonic-clonic in comparison to other seizure behaviors. Conclusion: A hierarchy behavior was observed during the kindling process when considering the first occurrence of seizure behaviors. We defined the first occurrence of restlessness, motionless, hind limb tonic extension and Straub’s tail behaviors as an early phase, myoclonic jerk as a borderline phase and tonic-clonic as a late phase of PTZ-induced kindling. Our results indicated an enhanced SVZ neurogenesis at the late phase of kindling. [GMJ.2019;8:e1511]

Molecular Docking, Synthesis and anti-HIV-1 Protease Activity of Novel Chalcones

2020 ◽  
Vol 26 (8) ◽  
pp. 802-814 ◽  
Author(s):  
Nemanja Turkovic ◽  
Branka Ivkovic ◽  
Jelena Kotur-Stevuljevic ◽  
Milica Tasic ◽  
Bojan Marković ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Molecular Docking ◽  
Chemical Synthesis ◽  
Protease Activity ◽  
Molecular Mechanisms ◽  
Replication Cycle ◽  
Low Molecular Weight ◽  
Chalcone Derivatives ◽  
Anti Hiv ◽  
Hiv 1

Background: Since the beginning of the HIV/AIDS epidemic, 75 million people have been infected with the HIV and about 32 million people have died of AIDS. Investigation of the molecular mechanisms critical to the HIV replication cycle led to the identification of potential drug targets for AIDS therapy. One of the most important discoveries is HIV-1 protease, an enzyme that plays an essential role in the replication cycle of HIV. Objective: The aim of the present study is to synthesize and investigate anti-HIV-1 protease activity of some chalcone derivatives with the hope of discovering new lead structure devoid drug resistance. Methods: 20 structurally similar chalcone derivatives were synthesized and their physico-chemical characterization was performed. Binding of chalcones to HIV-1 protease was investigated by fluorimetric assay. Molecular docking studies were conducted to understand the interactions. Results: The obtained results revealed that all compounds showed anti-HIV-1 protease activity. Compound C1 showed the highest inhibitory activity with an IC50 value of 0.001 μM, which is comparable with commercial product Darunavir. Conclusion: It is difficult to provide general principles of inhibitor design. Structural properties of the compounds are not the only consideration; ease of chemical synthesis, low molecular weight, bioavailability, and stability are also of crucial importance. Compared to commercial products the main advantage of compound C1 is the ease of chemical synthesis and low molecular weight. Furthermore, compound C1 has a structure that is different to peptidomimetics, which could contribute to its stability and bioavailability.

Nucleolin Improves Heart Function During Recovery From Myocardial Infarction by Modulating Macrophage Polarization

2021 ◽  
pp. 107424842198957
Author(s):  
Yuting Tang ◽  
Xiaofang Lin ◽  
Cheng Chen ◽  
Zhongyi Tong ◽  
Hui Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Early Phase ◽  
Heart Function ◽  
Macrophage Polarization ◽  
Late Phase ◽  
Macrophage Infiltration ◽  
Enzyme Linked Immunosorbent Assay ◽  
M2 Macrophage ◽  
M2 Macrophage Polarization ◽  
Nucleolin Expression

Background: Nucleolin has multiple functions within cell survival and proliferation pathways. Our previous studies have revealed that nucleolin can significantly reduce myocardial ischemia-reperfusion injury by promoting myocardial angiogenesis and reducing myocardial apoptosis. In this study, we attempted to determine the role of nucleolin in myocardial infarction (MI) injury recovery and the underlying mechanism. Methods: Male BALB/c mice aged 6–8 weeks were used to set up MI models by ligating the left anterior descending coronary artery. Nucleolin expression in the heart was downregulated by intramyocardial injection of a lentiviral vector expressing nucleolin-specific small interfering RNA. Macrophage infiltration and polarization were measured by real-time polymerase chain reaction, flow cytometry, and immunofluorescence. Cytokines were detected by enzyme-linked immunosorbent assay. Results: Nucleolin expression in myocardium after MI induction decreased a lot at early phase and elevated at late phase. Nucleolin knockdown impaired heart systolic and diastolic functions and decreased the survival rate after MI. Macrophage infiltration increased in the myocardium after MI. Most macrophages belonged to the M1 phenotype at early phase (2 days) and the M2 phenotype increased greatly at late phase after MI. Nucleolin knockdown in the myocardium led to a decrease in M2 macrophage polarization with no effect on macrophage infiltration after MI. Furthermore, Notch3 and STAT6, key regulators of M2 macrophage polarization, were upregulated by nucleolin in RAW 264.7 macrophages. Conclusions: Lack of nucleolin impaired heart function during recovery after MI by reducing M2 macrophage polarization. This finding probably points to a new therapeutic option for ischemic heart disease.

scholarly journals AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takao Watanabe ◽  
Yoshio Tokumoto ◽  
Kouji Joko ◽  
Kojiro Michitaka ◽  
Norio Horiike ◽  
...  
Keyword(s):  
Risk Factors ◽  
Confidence Interval ◽  
Early Phase ◽  
Late Phase ◽  
Previous History ◽  
Late Recurrence ◽  
Early Recurrence ◽  
Hazard Ratio ◽  
Post Treatment ◽  
Hcc Recurrence

Abstract Background An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment. Methods Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as ‘early recurrence’, and recurrence more than 1 year after as ‘late recurrence’. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated. Results Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026–1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96–0.99, p = 0.032) as a predictor of HCC recurrence in the late phase. Conclusion Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases.

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