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preLekára.sk / Odborné časopisy / PLOS Pathogens / 2015 - 6

Human Immunodeficiency Virus Type 1 Nef Inhibits Autophagy through Transcription Factor EB Sequestration

English version České info

Under basal conditions, the mammalian target of rapamycin (MTOR) phosphorylates transcription factor EB (TFEB) resulting in its cytoplasmic retention. When MTOR is inhibited, TFEB is dephosphorylated and translocated to the nucleus where it increases autophagy and lysosomal gene expression. As human immunodeficiency virus type 1 (HIV) Nef acts as an anti-autophagic maturation factor through interaction with beclin-1 (BECN1), we investigated the role of Nef and TFEB in the modulation of autophagy during HIV infection of human macrophages. We found that upon exposure to HIV, macrophages elicited an autophagic response through a toll-like receptor 8 (TLR8) and BECN1 dependent dephosphorylation and nuclear translocation of TFEB. However, once HIV infection is established, phosphorylation and cytoplasmic sequestration of TFEB as well as autophagy revert to pre-infection levels. Moreover, this reversion is dependent upon the presence of HIV Nef. Collectively, the data suggests that the interaction between HIV and TLR8 serves as a signal for autophagy induction that is dependent upon the dephosphorylation and nuclear translocation of TFEB. Once HIV establishes a productive infection, Nef binds BECN1 resulting in MTOR activation, TFEB phosphorylation and cytosolic sequestration and the inhibition of autophagy.

Vyšlo v časopise: Human Immunodeficiency Virus Type 1 Nef Inhibits Autophagy through Transcription Factor EB Sequestration. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1005018
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005018

Souhrn

Under basal conditions, the mammalian target of rapamycin (MTOR) phosphorylates transcription factor EB (TFEB) resulting in its cytoplasmic retention. When MTOR is inhibited, TFEB is dephosphorylated and translocated to the nucleus where it increases autophagy and lysosomal gene expression. As human immunodeficiency virus type 1 (HIV) Nef acts as an anti-autophagic maturation factor through interaction with beclin-1 (BECN1), we investigated the role of Nef and TFEB in the modulation of autophagy during HIV infection of human macrophages. We found that upon exposure to HIV, macrophages elicited an autophagic response through a toll-like receptor 8 (TLR8) and BECN1 dependent dephosphorylation and nuclear translocation of TFEB. However, once HIV infection is established, phosphorylation and cytoplasmic sequestration of TFEB as well as autophagy revert to pre-infection levels. Moreover, this reversion is dependent upon the presence of HIV Nef. Collectively, the data suggests that the interaction between HIV and TLR8 serves as a signal for autophagy induction that is dependent upon the dephosphorylation and nuclear translocation of TFEB. Once HIV establishes a productive infection, Nef binds BECN1 resulting in MTOR activation, TFEB phosphorylation and cytosolic sequestration and the inhibition of autophagy.

Zdroje

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Článek The Curious Road from Basic Pathogen Research to Clinical Translation
Článek From Cell and Organismal Biology to Drugs
Článek Adenovirus Tales: From the Cell Surface to the Nuclear Pore Complex
Článek A 21st Century Perspective of Poliovirus Replication
Článek Is Development of a Vaccine against Feasible?
Článek Waterborne Viruses: A Barrier to Safe Drinking Water
Článek Battling Phages: How Bacteria Defend against Viral Attack
Článek Archaea in and on the Human Body: Health Implications and Future Directions
Článek Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche
Článek Natural Variants of the KPC-2 Carbapenemase have Evolved Increased Catalytic Efficiency for Ceftazidime Hydrolysis at the Cost of Enzyme Stability
Článek Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers
Článek The Mammalian Cell Cycle Regulates Parvovirus Nuclear Capsid Assembly
Článek Host Reticulocytes Provide Metabolic Reservoirs That Can Be Exploited by Malaria Parasites
Článek The Proteome of the Isolated Containing Vacuole Reveals a Complex Trafficking Platform Enriched for Retromer Components
Článek NK-, NKT- and CD8-Derived IFNγ Drives Myeloid Cell Activation and Erythrophagocytosis, Resulting in Trypanosomosis-Associated Acute Anemia
Článek Successes and Challenges on the Road to Cure Hepatitis C
Článek BRCA1 Regulates IFI16 Mediated Nuclear Innate Sensing of Herpes Viral DNA and Subsequent Induction of the Innate Inflammasome and Interferon-β Responses
Článek A Structural and Functional Comparison Between Infectious and Non-Infectious Autocatalytic Recombinant PrP Conformers
Článek Phosphorylation of the Peptidoglycan Synthase PonA1 Governs the Rate of Polar Elongation in Mycobacteria
Článek Sequence-Specific Fidelity Alterations Associated with West Nile Virus Attenuation in Mosquitoes
Článek EBV BART MicroRNAs Target Multiple Pro-apoptotic Cellular Genes to Promote Epithelial Cell Survival
Článek Single-Cell and Single-Cycle Analysis of HIV-1 Replication
Článek TRIM32 Senses and Restricts Influenza A Virus by Ubiquitination of PB1 Polymerase
Článek The Herpes Simplex Virus Protein pUL31 Escorts Nucleocapsids to Sites of Nuclear Egress, a Process Coordinated by Its N-Terminal Domain
Článek Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study
Článok vyšiel v časopise

PLOS Pathogens

2015 Číslo 6
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Autori: doc. MUDr. David Zemánek, Ph.D., MUDr. Anna Chaloupka, Ph.D.
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