scholarly journals BPIFB3 interacts with ARFGAP1 and TMED9 to regulate non-canonical autophagy and RNA virus infection

2020 ◽  
Author(s):  
Azia S. Evans ◽  
Nicholas J. Lennemann ◽  
Carolyn B. Coyne
Keyword(s):  
Mammalian Cells ◽  
Viral Infections ◽  
Rna Virus ◽  
Cellular Autophagy ◽  
Essential Components ◽  
Important Regulator ◽  
Summary Statement ◽  
Autophagy Pathway ◽  
Cellular Components

AbstractAutophagy is a degradative cellular pathway that targets cytoplasmic contents and organelles for turnover by the lysosome. Various autophagy pathways play key roles in the clearance of viral infections, and many families of viruses have developed unique methods for avoiding degradation. Some positive stranded RNA viruses, such as enteroviruses and flaviviruses, usurp the autophagic pathway to promote their own replication. We previously identified the endoplasmic reticulum-localized protein BPIFB3 as an important regulator of non-canonical autophagy that uniquely impacts the replication of enteroviruses and flaviviruses. Here, we find that many components of the canonical autophagy machinery are not required for BPIFB3-regulated autophagy and identify the host factors that facilitate its role in the replication of enteroviruses and flaviviruses. Using proximity-dependent biotinylation (BioID) followed by mass spectrometry, we identify ARFGAP1 and TMED9 as two cellular components that interact with BPIFB3 to regulate autophagy and viral replication. Importantly, our data demonstrate that non-canonical autophagy in mammalian cells can be controlled outside of the traditional pathway regulators and define the role of two proteins in BPIFB3-mediated non-canonical autophagy.Summary StatementBPIFB3 is a regulator of a non-canonical cellular autophagy pathway that impacts the replication of enteroviruses and flaviviruses. Here we define ARFGAP1 and TMED9 as essential components of this pathway.

scholarly journals BPIFB3 interacts with ARFGAP1 and TMED9 to regulate non-canonical autophagy and RNA virus infection

2020 ◽  
pp. jcs.251835
Author(s):  
Azia S. Evans ◽  
Nicholas J. Lennemann ◽  
Carolyn B. Coyne
Keyword(s):  
Mass Spectrometry ◽  
Mammalian Cells ◽  
Viral Infections ◽  
Rna Viruses ◽  
Rna Virus ◽  
Negative Regulator ◽  
Host Factors ◽  
Important Negative Regulator ◽  
Cellular Components

Autophagy is a degradative cellular pathway that targets cytoplasmic contents and organelles for turnover by the lysosome. Various autophagy pathways play key roles in the clearance of viral infections, and many families of viruses have developed unique methods for avoiding degradation. Some positive stranded RNA viruses, such as enteroviruses and flaviviruses, usurp the autophagic pathway to promote their own replication. We previously identified the endoplasmic reticulum-localized protein BPIFB3 as an important negative regulator of non-canonical autophagy that uniquely impacts the replication of enteroviruses and flaviviruses. Here, we find that many components of the canonical autophagy machinery are not required for BPIFB3 depletion induced autophagy and identify the host factors that facilitate its role in the replication of enteroviruses and flaviviruses. Using proximity-dependent biotinylation (BioID) followed by mass spectrometry, we identify ARFGAP1 and TMED9 as two cellular components that interact with BPIFB3 to regulate autophagy and viral replication. Importantly, our data demonstrate that non-canonical autophagy in mammalian cells can be controlled outside of the traditional pathway regulators and define the role of two proteins in BPIFB3 depletion mediated non-canonical autophagy.

scholarly journals Protective Features of Autophagy in Pulmonary Infection and Inflammatory Diseases

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 123 ◽  
Author(s):  
Kui Wang ◽  
Yi Chen ◽  
Pengju Zhang ◽  
Ping Lin ◽  
Na Xie ◽  
...  
Keyword(s):  
Pulmonary Infection ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Autophagy Pathway ◽  
Pulmonary Arterial ◽  
Cellular Components ◽  
Cellular Stressors

Autophagy is a highly conserved catabolic process involving autolysosomal degradation of cellular components, including protein aggregates, damaged organelles (such as mitochondria, endoplasmic reticulum, and others), as well as various pathogens. Thus, the autophagy pathway represents a major adaptive response for the maintenance of cellular and tissue homeostasis in response to numerous cellular stressors. A growing body of evidence suggests that autophagy is closely associated with diverse human diseases. Specifically, acute lung injury (ALI) and inflammatory responses caused by bacterial infection or xenobiotic inhalation (e.g., chlorine and cigarette smoke) have been reported to involve a spectrum of alterations in autophagy phenotypes. The role of autophagy in pulmonary infection and inflammatory diseases could be protective or harmful dependent on the conditions. In this review, we describe recent advances regarding the protective features of autophagy in pulmonary diseases, with a focus on ALI, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), tuberculosis, pulmonary arterial hypertension (PAH) and cystic fibrosis.

scholarly journals Coxsackievirus infection induces a non-canonical autophagy independent of the ULK and PI3K complexes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yasir Mohamud ◽  
Junyan Shi ◽  
Hui Tang ◽  
Pinhao Xiang ◽  
Yuan Chao Xue ◽  
...  
Keyword(s):  
Rna Virus ◽  
Transmembrane Protein ◽  
Kinase Domain ◽  
Conjugation System ◽  
Culture Cells ◽  
Cvb3 Infection ◽  
Cellular Machinery ◽  
Autophagy Pathway ◽  
Substrate Binding Domain

Abstract Coxsackievirus B3 (CVB3) is a single-stranded positive RNA virus that usurps cellular machinery, including the evolutionarily anti-viral autophagy pathway, for productive infections. Despite the emergence of double-membraned autophagosome-like vesicles during CVB3 infection, very little is known about the mechanism of autophagy initiation. In this study, we investigated the role of established autophagy factors in the initiation of CVB3-induced autophagy. Using siRNA-mediated gene-silencing and CRISPR-Cas9-based gene-editing in culture cells, we discovered that CVB3 bypasses the ULK1/2 and PI3K complexes to trigger autophagy. Moreover, we found that CVB3-induced LC3 lipidation occurred independent of WIPI2 and the transmembrane protein ATG9 but required components of the late-stage ubiquitin-like ATG conjugation system including ATG5 and ATG16L1. Remarkably, we showed the canonical autophagy factor ULK1 was cleaved through the catalytic activity of the viral proteinase 3C. Mutagenesis experiments identified the cleavage site of ULK1 after Q524, which separates its N-terminal kinase domain from C-terminal substrate binding domain. Finally, we uncovered PI4KIIIβ (a PI4P kinase), but not PI3P or PI5P kinases as requisites for CVB3-induced LC3 lipidation. Taken together, our studies reveal that CVB3 initiates a non-canonical form of autophagy that bypasses ULK1/2 and PI3K signaling pathways to ultimately converge on PI4KIIIβ- and ATG5–ATG12–ATG16L1 machinery.

scholarly journals Effects of APOBEC3G's Cytidine Deaminase Activity on Retroviral Evolution

2021 ◽  
Vol 15 ◽  
pp. 55-61
Author(s):  
Mary-Benedicta Obikili
Keyword(s):  
Viral Infection ◽  
Mammalian Cells ◽  
Viral Infections ◽  
Cytidine Deaminase ◽  
Viral Evolution ◽  
Cytidine Deaminase Activity ◽  
Immunodeficiency Virus ◽  
Potential Impact ◽  
Retroviral Infections

Apolipoprotein B editing complex (APOBEC3/A3) genes are found in mammalian cells. In primates, there are 7 APOBEC3 genes, namely, 3A, 3B, 3C, 3DE, 3F, 3G, and 3H. Previous research has shown that A3 proteins help to inhibit viral infection via their cytidine deaminase activity. However, it has also been found that A3 proteins could also lead to viral evolution, where viruses such as HIV (Human Immunodeficiency Virus) instead gain beneficial mutations that enable them to overcome the antiviral activity of A3 proteins, gain resistance to certain drugs used for treating viral infections and escape recognition by the immune system. This paper is a review article summarizing the role of A3G on viral infection and evolution, and the potential impact viral evolution could have in treatment of retroviral infections such as HIV.

scholarly journals Poly(A) binding protein is required for mRNP remodeling to form P-bodies in mammalian cells

2021 ◽  
Author(s):  
Jingwei Xie ◽  
Yu Chen ◽  
Xiaoyu Wei ◽  
Guennadi Kozlov
Keyword(s):  
Mammalian Cells ◽  
Binding Protein ◽  
Stress Granules ◽  
Body Formation ◽  
P Bodies ◽  
Rna Granules ◽  
Cellular Processes ◽  
Early Stages ◽  
Summary Statement

AbstractCompartmentalization of mRNA through formation of RNA granules is involved in many cellular processes, yet it is not well understood. mRNP complexes undergo dramatic changes in protein compositions, reflected by markers of P-bodies and stress granules. Here, we show that PABPC1, albeit absent in P-bodies, plays important role in P-body formation. Depletion of PABPC1 decreases P-body population in unstressed cells. Upon stress in PABPC1 depleted cells, individual P-bodies fail to form and instead P-body proteins assemble on PABPC1-containing stress granules. We hypothesize that mRNP recruit proteins via PABPC1 to assemble P-bodies, before PABPC1 is displaced from mRNP. Further, we demonstrate that GW182 can mediate P-body assembly. These findings help us understand the early stages of mRNP remodeling and P-body formation.Summary statementA novel role of poly(A) binding protein is reported in P-body formation

scholarly journals Molecular Insights into the Multifunctional Role of Natural Compounds: Autophagy Modulation and Cancer Prevention

2020 ◽  
Author(s):  
Md. Ataur Rahman ◽  
Hasanur Rahman ◽  
Md. Shahadat Hossain ◽  
Partha Biswas ◽  
Rokibul Islam ◽  
...  
Keyword(s):  
Side Effects ◽  
Cancer Treatment ◽  
Cancer Prevention ◽  
Stress Responses ◽  
Natural Compounds ◽  
Degradation Pathway ◽  
Synthetic Chemicals ◽  
Cellular Autophagy ◽  
Autophagy Pathway

Autophagy is a vacuolar, lysosomal degradation pathway for injured and damaged protein molecules and organelles in eukaryotic cells, which is controlled by nutrients and stress responses. Dysregulation of cellular autophagy may lead to various diseases such as neurodegenerative disease, obesity, cardiovascular disease, diabetes, and malignancy. Recently, natural compounds have come to attention for being able to modulate the autophagy pathway in cancer prevention, although the prospective role of autophagy in cancer treatment is very complex and not yet clearly elucidated. Numerous synthetic chemicals have been identified that modulate autophagy and are favorable candidates for cancer treatment, but they have adverse side effects. Therefore, different phytochemicals, which include natural compounds and their derivatives, have attracted significant attention for use as autophagy modulators in cancer treatment with minimal side effects. In the current review, we discuss the promising role of natural compounds in modulating the autophagy pathway to control and prevent cancer, and provide possible therapeutic options.

Autophagy in Plant-Virus Interactions

2020 ◽  
Vol 7 (1) ◽  
pp. 403-419 ◽  
Author(s):  
Meng Yang ◽  
Asigul Ismayil ◽  
Yule Liu
Keyword(s):  
Plant Virus ◽  
Defense Mechanism ◽  
Degradation Pathway ◽  
Plant Viruses ◽  
Antiviral Defense ◽  
Autophagy Pathway ◽  
Virus Interactions ◽  
Plant Pathogen Interactions ◽  
Cellular Components

Autophagy is a conserved vacuole/lysosome-mediated degradation pathway for clearing and recycling cellular components including cytosol, macromolecules, and dysfunctional organelles. In recent years, autophagy has emerged to play important roles in plant-pathogen interactions. It acts as an antiviral defense mechanism in plants. Moreover, increasing evidence shows that plant viruses can manipulate, hijack, or even exploit the autophagy pathway to promote pathogenesis, demonstrating the pivotal role of autophagy in the evolutionary arms race between hosts and viruses. In this review, we discuss recent findings about the antiviral and proviral roles of autophagy in plant-virus interactions.

scholarly journals Exosome Biogenesis and Biological Function in Response to Viral Infections

2018 ◽  
Vol 12 (1) ◽  
pp. 134-148 ◽  
Author(s):  
Brennetta J. Crenshaw ◽  
Linlin Gu ◽  
Brian Sims ◽  
Qiana L. Matthews
Keyword(s):  
Protein Trafficking ◽  
Viral Infections ◽  
Rna Virus ◽  
Cellular Protein ◽  
Molecular Characteristics ◽  
Exosome Biogenesis ◽  
Pathogen Response ◽  
Viral Hijacking ◽  
The Impact

Introduction: Exosomes are extracellular vesicles that originate as intraluminal vesicles during the process of multivescular body formation. Exosomes mediate intercellular transfer of functional proteins, lipids, and RNAs. The investigation into the formation and role of exosomes in viral infections is still being elucidated. Exosomes and several viruses share similar structural and molecular characteristics. Explanation: It has been documented that viral hijacking exploits the exosomal pathway and mimics cellular protein trafficking. Exosomes released from virus-infected cells contain a variety of viral and host cellular factors that are able to modify recipient host cell responses. Recent studies have demonstrated that exosomes are crucial components in the pathogenesis of virus infection. Exosomes also allow the host to produce effective immunity against pathogens by activating antiviral mechanisms and transporting antiviral factors between adjacent cells. Conclusion: Given the ever-growing roles and importance of exosomes in both host and pathogen response, this review will address the impact role of exosome biogenesis and composition after DNA, RNA virus, on Retrovirus infections. This review also will also address how exosomes can be used as therapeutic agents as well as a vaccine vehicles.

scholarly journals Mitophagy in Yeast: Molecular Mechanism and Regulation

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3569
Author(s):  
Aleksei Innokentev ◽  
Tomotake Kanki
Keyword(s):  
Molecular Mechanism ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Outer Membrane Proteins ◽  
Physiological Role ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Homeostasis ◽  
Mitochondrial Ros ◽  
Cellular Components

Mitophagy is a type of autophagy that selectively degrades mitochondria. Mitochondria, known as the “powerhouse of the cell”, supply the majority of the energy required by cells. During energy production, mitochondria produce reactive oxygen species (ROS) as byproducts. The ROS damages mitochondria, and the damaged mitochondria further produce mitochondrial ROS. The increased mitochondrial ROS damages cellular components, including mitochondria themselves, and leads to diverse pathologies. Accordingly, it is crucial to eliminate excessive or damaged mitochondria to maintain mitochondrial homeostasis, in which mitophagy is believed to play a major role. Recently, the molecular mechanism and physiological role of mitophagy have been vigorously studied in yeast and mammalian cells. In yeast, Atg32 and Atg43, mitochondrial outer membrane proteins, were identified as mitophagy receptors in budding yeast and fission yeast, respectively. Here we summarize the molecular mechanisms of mitophagy in yeast, as revealed by the analysis of Atg32 and Atg43, and review recent progress in our understanding of mitophagy induction and regulation in yeast.

RNA Coronaviruses’ Outbreaks: Recent Progress on the SARS-CoV-2 Pandemic Diagnostic Tests, Vaccination and Therapeutics

2021 ◽  
Vol 21 ◽  
Author(s):  
Ghadeer A. R. Y. Suaifan ◽  
Bayan A. Alkhawaja ◽  
Aya A. M. Mohammed
Keyword(s):  
Viral Infections ◽  
Rna Virus ◽  
Infectious Agent ◽  
The Novel ◽  
Clinical Prognosis ◽  
High Profile ◽  
Intervention Measures ◽  
Diagnostic Approaches ◽  
Novel Coronavirus

: Coronaviruses are RNA-infective viruses that could be considered principal players in universal high-profile outbreaks, namely the Severe Acute Respiratory Syndrome (SARS, 2002-2003), the Middle East Respiratory Syndrome (MERS, 2012) and the continuing novel coronavirus disease (COVID-19, 2019) pandemic. RNA coronaviruses infections raise public health concerns with infections’ severity ranging from serious pandemics and highly contagious infections to common influenza episodes. With a wide consensus concerning the seminal role of early detection of the infectious agent on the clinical prognosis, recent technological endeavors have facilitated the rapid, sensitive and specific diagnosis of viral infections. Given that the burst of confirmed cases of the novel coronavirus disease 2019 (COVID-19) are climbing steeply, and we are amid this pandemic, this work will center at the respiratory RNA-viruses outbreaks, including the three coronaviruses-related pandemics, emphasizing on the approved diagnostic approaches, outlining therapeutic clinical trials as well as vaccine candidates. Based on the accumulated data and knowledge on the previous RNA-virus outbreaks, this review aspires to link the current intervention measures against SARS-CoV-2 infection with the previous interventions and to provide a roadmap for any possible future measures.

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