Abstract
The central events of HIV-1 life cycle occur at the nuclear level where the viral genome is integrated into the host cellular DNA in order to be expressed and replicated. The viral pre-integration complexes (PICs) are actively transported in the nuclear compartment where integration occurs in specific regions of the cellular chromatin. Similar to all viruses, HIV-1 encodes for a limited number of proteins that are insufficient to produce new viral progenies. Several cellular pathways are thus hijacked by HIV-1 to efficiently complete the replication cycle. The majority of viral proteins are substrates for cellular kinases indicating a pivotal role of these cellular enzymes at multiple steps of the HIV-1 life cycle. The nuclear biology of the cell is highly controlled by kinases (nuclear transport, DNA replication, repair and transcription) and many of these kinases also sustain the viral nuclear events. This review summarizes our current knowledge on kinases that are involved in HIV-1 replication cycle at the nuclear level, both directly through their catalytic activity on viral proteins and indirectly being activated by the virus. Among viral proteins directly modified by kinases is integrase (IN) the factor that catalyzes the integration of HIV-1 in the cellular genome. Notably, this recent discovery may shed light onto mechanisms underlying the different susceptibility of the main cell types targeted by HIV-1 (CD-4+ T-cell) depending on their activation status. Alternatively, kinases may act indirectly such as in the case of DNA repair factors activated following HIV-1 infection and demonstrated to regulate the viral life cycle.
Finally, inhibition of cellular kinases interacting with HIV-1 at the nuclear level has been shown to severely affect the viral replication cycle, thus suggesting potential new therapeutic approaches.
Keywords: Capsid, HIV-1, Integrase, Kinases, Nucleus, Phosphorylation, Matrix, Rev, Tat, Vpr
Current Medicinal Chemistry
Title: Role of Phosphorylation in the Nuclear Biology of HIV-1
Volume: 18 Issue: 19
Author(s): A. C. Francis, C. Di Primio, A. Allouch and A. Cereseto
Affiliation:
Keywords: Capsid, HIV-1, Integrase, Kinases, Nucleus, Phosphorylation, Matrix, Rev, Tat, Vpr
Abstract: The central events of HIV-1 life cycle occur at the nuclear level where the viral genome is integrated into the host cellular DNA in order to be expressed and replicated. The viral pre-integration complexes (PICs) are actively transported in the nuclear compartment where integration occurs in specific regions of the cellular chromatin. Similar to all viruses, HIV-1 encodes for a limited number of proteins that are insufficient to produce new viral progenies. Several cellular pathways are thus hijacked by HIV-1 to efficiently complete the replication cycle. The majority of viral proteins are substrates for cellular kinases indicating a pivotal role of these cellular enzymes at multiple steps of the HIV-1 life cycle. The nuclear biology of the cell is highly controlled by kinases (nuclear transport, DNA replication, repair and transcription) and many of these kinases also sustain the viral nuclear events. This review summarizes our current knowledge on kinases that are involved in HIV-1 replication cycle at the nuclear level, both directly through their catalytic activity on viral proteins and indirectly being activated by the virus. Among viral proteins directly modified by kinases is integrase (IN) the factor that catalyzes the integration of HIV-1 in the cellular genome. Notably, this recent discovery may shed light onto mechanisms underlying the different susceptibility of the main cell types targeted by HIV-1 (CD-4+ T-cell) depending on their activation status. Alternatively, kinases may act indirectly such as in the case of DNA repair factors activated following HIV-1 infection and demonstrated to regulate the viral life cycle.
Finally, inhibition of cellular kinases interacting with HIV-1 at the nuclear level has been shown to severely affect the viral replication cycle, thus suggesting potential new therapeutic approaches.
Export Options
About this article
Cite this article as:
C. Francis A., Di Primio C., Allouch A. and Cereseto A., Role of Phosphorylation in the Nuclear Biology of HIV-1, Current Medicinal Chemistry 2011; 18 (19) . https://dx.doi.org/10.2174/092986711796150478
DOI https://dx.doi.org/10.2174/092986711796150478 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Multiple Sclerosis – Established and Novel Therapeutic Approaches
Central Nervous System Agents in Medicinal Chemistry Novel Oral Anticoagulants for Venous Thromboembolism with Special Emphasis on Risk of Hemorrhagic Complications and Reversal Agents
Current Drug Therapy Cell Cycle and Cancer: The G1 Restriction Point and the G1 / S Transition
Current Genomics Naturally Occurring Calanolides: An Update on Their Anti-HIV Potential and Total Syntheses
Recent Patents on Biotechnology Transcriptional Regulation in Mammalian Pituitary Development and Disease
Current Genomics Fe-S Proteins Acting as Redox Switch: New Key Actors of Cellular Adaptive Responses
Current Chemical Biology Role of the Osteochondral Unit in the Pathogenesis of Osteoarthritis: Focus on the Potential Use of Clodronate
Current Rheumatology Reviews Surfactant Proteins in Smoking-Related Lung Disease
Current Topics in Medicinal Chemistry The Pathophysiology of Heme in the Brain
Current Alzheimer Research Hematopoietic Colony Stimulating Factors in Cardiovascular and Pulmonary Remodeling: Promoters or Inhibitors?
Current Pharmaceutical Design Modulation of Energy Intake and Expenditure Due to Habitual Physical Exercise
Current Pharmaceutical Design Apoptosis: A Key in Neurodegenerative Disorders
Current Neurovascular Research Molecular and Biochemical Changes of the Cardiovascular System due to Smoking Exposure
Current Pharmaceutical Design Mitochondrial Biogenesis in Health and Disease. Molecular and Therapeutic Approaches
Current Pharmaceutical Design Targeting Epigenetics in Nervous System Disease
CNS & Neurological Disorders - Drug Targets Recent Development and Future Perspective of Antitubercular Therapy
Anti-Infective Agents in Medicinal Chemistry The Ovary Feels Fine when Paracrine and Autocrine Networks Cooperate with Gonadotropins in the Regulation of Folliculogenesis
Current Pharmaceutical Design Melatonin in Cardiac Ischemia/Reperfusion-Induced Mitochondrial Adaptive Changes
Cardiovascular & Hematological Disorders-Drug Targets The Emerging Role of MicroRNA in Schizophrenia
CNS & Neurological Disorders - Drug Targets γ-Secretase as a Therapeutic Target for the Treatment of Alzheimers Disease
Current Pharmaceutical Design