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Apoptosis, autophagy and unfolded protein response pathways in Arbovirus replication and pathogenesis.

Iranpour M, Moghadam AR, Yazdi M, Ande SR, Alizadeh J, Wiechec E, Lindsay R, Drebot M, Coombs KM, Ghavami S - Expert Rev Mol Med (2016)

Bottom Line: Recently, a few successful approaches toward production of effective vaccines against some of these pathogens have been developed, but treatment and prevention of the resulting diseases remain a major health and research concern.The arbovirus infection and replication processes are complex, and many factors are involved in their regulation.In this review, we focus on the importance of these pathways in the arbovirus replication and infection processes.

View Article: PubMed Central - PubMed

Affiliation: Zoonotic Diseases and Special Pathogens,National Microbiology Laboratory,Public Health Agency of Canada,1015 Arlington St.,Winnipeg,Manitoba,Canada.

ABSTRACT
Arboviruses are pathogens that widely affect the health of people in different communities around the world. Recently, a few successful approaches toward production of effective vaccines against some of these pathogens have been developed, but treatment and prevention of the resulting diseases remain a major health and research concern. The arbovirus infection and replication processes are complex, and many factors are involved in their regulation. Apoptosis, autophagy and the unfolded protein response (UPR) are three mechanisms that are involved in pathogenesis of many viruses. In this review, we focus on the importance of these pathways in the arbovirus replication and infection processes. We provide a brief introduction on how apoptosis, autophagy and the UPR are initiated and regulated, and then discuss the involvement of these pathways in regulation of arbovirus pathogenesis.

No MeSH data available.


Related in: MedlinePlus

Graphic representation of autophagy. Autophagy is a process for the degradation and recycling of damaged or unnecessary cellular compartments, which has several tightly regulated steps including induction, nucleation, expansion and completion, fusion and degradation. The mTOR is known as the key regulator of autophagy induction and can be suppressed by ULK1, leading to trigger VPS34-Beclin 1-class III PI3-kinase complex. Several different membrane pools contribute to the formation of the phagophore. The Atg proteins (Atg2, Atg9, Atg18) are essential for phagophore formation. The ATG and LC3 conjugation system also contribute in autophagosome membrane formation and elongation. The autophagolysosome then is formed by fusion of the autophagosome with a lysosome to degrade and reuse the compounds. ATG, autophagy-related genes; mTOR, mammalian target of rapamycin.
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fig03: Graphic representation of autophagy. Autophagy is a process for the degradation and recycling of damaged or unnecessary cellular compartments, which has several tightly regulated steps including induction, nucleation, expansion and completion, fusion and degradation. The mTOR is known as the key regulator of autophagy induction and can be suppressed by ULK1, leading to trigger VPS34-Beclin 1-class III PI3-kinase complex. Several different membrane pools contribute to the formation of the phagophore. The Atg proteins (Atg2, Atg9, Atg18) are essential for phagophore formation. The ATG and LC3 conjugation system also contribute in autophagosome membrane formation and elongation. The autophagolysosome then is formed by fusion of the autophagosome with a lysosome to degrade and reuse the compounds. ATG, autophagy-related genes; mTOR, mammalian target of rapamycin.

Mentions: The first step in autophagy (see Fig. 3) involves formation and expansion of a double-membrane structure, which is called the ‘isolation membrane’ or ‘phagophore’. The edges of this membrane eventually fuse to form a new double membrane-bound vacuole, known as the autophagosome that sequesters the cytoplasmic cargo. The autophagolysosome is formed by fusion of the autophagosome with a lysosome and lysosomal contents are degraded by hydrolytic enzymes (Refs 115, 116, 117, 118). As a result of degradation, nucleotides, amino acids and free fatty acids (FFAs) are generated and then reused for energy metabolism, macromolecular production and biosynthesis (Refs 119, 120). It is assumed that the different steps in macroautophagy are mediated by autophagy-related genes (ATG), which encode proteins involved in autophagy (Refs 121, 122). These proteins have been classified into five different functional categories: (i) a protein serine/threonine kinase complex that responds to upstream events such as target of rapamycin (TOR) kinase (Atg1/ULK1, Atg13 and Atg17); (ii) a lipid kinase group that controls vesicle nucleation (Atg6/Beclin1, Atg14, Vps34/PI3KC3 and Vps15); (iii) two ubiquitin-like conjugation pathways that stimulate vesicle expansion (the Atg8 and Atg12 conjugation systems); (iv) a recycling pathway that is required for disassembly of Atg proteins (Atg2, Atg9, Atg18); and (v) vacuolar permeases that permit the efflux of amino acids from the degradative compartment (Atg22) (Refs 93, 119). The mammalian TOR (mTOR) kinase acts as a negative regulator of autophagy and is a central controller of cell growth, aging and proliferation (Refs 123, 124). Under starvation conditions, inhibited mTOR induces autophagy through phosphorylation of the Ulk1-Atg13-FIP200-Atg101 complex (Refs 125, 126), leading to localization of Ulk1/2 and Atg13 to the autophagic isolation membrane (Refs 127, 128). During the initiation step of autophagy, Beclin 1 interacts with Vps34, which contributes to Atg protein recruitment and autophagosome nucleation (Refs 129, 130). Interaction with various Beclin-1-interacting proteins facilitates the coordination of these events (Ref. 131). LC3, the mammalian ortholog of Atg8, is cleaved by Atg4 and then conjugated to the polar head of phosphatidylethanolamine (PE) to generate LC3-II, which is necessary during the elongation step of autophagy (Refs 132, 133). Hence, the autophagosome is regulated in response to the Beclin-1/Vps34/UVRAG complex, known as the maturation step (Refs 134, 135, 136). An overview of autophagy is summarised in Figure 3.Figure 3.


Apoptosis, autophagy and unfolded protein response pathways in Arbovirus replication and pathogenesis.

Iranpour M, Moghadam AR, Yazdi M, Ande SR, Alizadeh J, Wiechec E, Lindsay R, Drebot M, Coombs KM, Ghavami S - Expert Rev Mol Med (2016)

Graphic representation of autophagy. Autophagy is a process for the degradation and recycling of damaged or unnecessary cellular compartments, which has several tightly regulated steps including induction, nucleation, expansion and completion, fusion and degradation. The mTOR is known as the key regulator of autophagy induction and can be suppressed by ULK1, leading to trigger VPS34-Beclin 1-class III PI3-kinase complex. Several different membrane pools contribute to the formation of the phagophore. The Atg proteins (Atg2, Atg9, Atg18) are essential for phagophore formation. The ATG and LC3 conjugation system also contribute in autophagosome membrane formation and elongation. The autophagolysosome then is formed by fusion of the autophagosome with a lysosome to degrade and reuse the compounds. ATG, autophagy-related genes; mTOR, mammalian target of rapamycin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836210&req=5

fig03: Graphic representation of autophagy. Autophagy is a process for the degradation and recycling of damaged or unnecessary cellular compartments, which has several tightly regulated steps including induction, nucleation, expansion and completion, fusion and degradation. The mTOR is known as the key regulator of autophagy induction and can be suppressed by ULK1, leading to trigger VPS34-Beclin 1-class III PI3-kinase complex. Several different membrane pools contribute to the formation of the phagophore. The Atg proteins (Atg2, Atg9, Atg18) are essential for phagophore formation. The ATG and LC3 conjugation system also contribute in autophagosome membrane formation and elongation. The autophagolysosome then is formed by fusion of the autophagosome with a lysosome to degrade and reuse the compounds. ATG, autophagy-related genes; mTOR, mammalian target of rapamycin.
Mentions: The first step in autophagy (see Fig. 3) involves formation and expansion of a double-membrane structure, which is called the ‘isolation membrane’ or ‘phagophore’. The edges of this membrane eventually fuse to form a new double membrane-bound vacuole, known as the autophagosome that sequesters the cytoplasmic cargo. The autophagolysosome is formed by fusion of the autophagosome with a lysosome and lysosomal contents are degraded by hydrolytic enzymes (Refs 115, 116, 117, 118). As a result of degradation, nucleotides, amino acids and free fatty acids (FFAs) are generated and then reused for energy metabolism, macromolecular production and biosynthesis (Refs 119, 120). It is assumed that the different steps in macroautophagy are mediated by autophagy-related genes (ATG), which encode proteins involved in autophagy (Refs 121, 122). These proteins have been classified into five different functional categories: (i) a protein serine/threonine kinase complex that responds to upstream events such as target of rapamycin (TOR) kinase (Atg1/ULK1, Atg13 and Atg17); (ii) a lipid kinase group that controls vesicle nucleation (Atg6/Beclin1, Atg14, Vps34/PI3KC3 and Vps15); (iii) two ubiquitin-like conjugation pathways that stimulate vesicle expansion (the Atg8 and Atg12 conjugation systems); (iv) a recycling pathway that is required for disassembly of Atg proteins (Atg2, Atg9, Atg18); and (v) vacuolar permeases that permit the efflux of amino acids from the degradative compartment (Atg22) (Refs 93, 119). The mammalian TOR (mTOR) kinase acts as a negative regulator of autophagy and is a central controller of cell growth, aging and proliferation (Refs 123, 124). Under starvation conditions, inhibited mTOR induces autophagy through phosphorylation of the Ulk1-Atg13-FIP200-Atg101 complex (Refs 125, 126), leading to localization of Ulk1/2 and Atg13 to the autophagic isolation membrane (Refs 127, 128). During the initiation step of autophagy, Beclin 1 interacts with Vps34, which contributes to Atg protein recruitment and autophagosome nucleation (Refs 129, 130). Interaction with various Beclin-1-interacting proteins facilitates the coordination of these events (Ref. 131). LC3, the mammalian ortholog of Atg8, is cleaved by Atg4 and then conjugated to the polar head of phosphatidylethanolamine (PE) to generate LC3-II, which is necessary during the elongation step of autophagy (Refs 132, 133). Hence, the autophagosome is regulated in response to the Beclin-1/Vps34/UVRAG complex, known as the maturation step (Refs 134, 135, 136). An overview of autophagy is summarised in Figure 3.Figure 3.

Bottom Line: Recently, a few successful approaches toward production of effective vaccines against some of these pathogens have been developed, but treatment and prevention of the resulting diseases remain a major health and research concern.The arbovirus infection and replication processes are complex, and many factors are involved in their regulation.In this review, we focus on the importance of these pathways in the arbovirus replication and infection processes.

View Article: PubMed Central - PubMed

Affiliation: Zoonotic Diseases and Special Pathogens,National Microbiology Laboratory,Public Health Agency of Canada,1015 Arlington St.,Winnipeg,Manitoba,Canada.

ABSTRACT
Arboviruses are pathogens that widely affect the health of people in different communities around the world. Recently, a few successful approaches toward production of effective vaccines against some of these pathogens have been developed, but treatment and prevention of the resulting diseases remain a major health and research concern. The arbovirus infection and replication processes are complex, and many factors are involved in their regulation. Apoptosis, autophagy and the unfolded protein response (UPR) are three mechanisms that are involved in pathogenesis of many viruses. In this review, we focus on the importance of these pathways in the arbovirus replication and infection processes. We provide a brief introduction on how apoptosis, autophagy and the UPR are initiated and regulated, and then discuss the involvement of these pathways in regulation of arbovirus pathogenesis.

No MeSH data available.


Related in: MedlinePlus