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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 ER stress and virus replication. ER stress is enhanced in the viral infected cells and activates UPR proteins (e.g. PERK, ATF6, and IRE1). Activated PERK leads to induce ATF4 via phosphorylation of eIF2α, causing attenuation of translation and inducing genes encoding CHOP. Upon IRE1 activation, TRAF2 and sXBPmRNA1 splicing are initiated in the cytoplasm, subsequently leading to activation of UPR target genes. The degradation of ATF6 is increased through recruitment of ATF6, a UPR sensor. ATF6 translocates to the Golgi and is cleaved to a nucleus targeting form that promotes expression of UPR-responsive genes. The consequences of UPR activation are necessary for viral replication and pathogenesis. ATF, activating transcription factor; CHOP, C/EBP homologous protein; ER, endoplasmic reticulum; IRE1, inositol-requiring enzyme; PERK, protein kinase RNA like ER kinase; UPR, unfolded protein response.
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fig05: Graphic representation of ER stress and virus replication. ER stress is enhanced in the viral infected cells and activates UPR proteins (e.g. PERK, ATF6, and IRE1). Activated PERK leads to induce ATF4 via phosphorylation of eIF2α, causing attenuation of translation and inducing genes encoding CHOP. Upon IRE1 activation, TRAF2 and sXBPmRNA1 splicing are initiated in the cytoplasm, subsequently leading to activation of UPR target genes. The degradation of ATF6 is increased through recruitment of ATF6, a UPR sensor. ATF6 translocates to the Golgi and is cleaved to a nucleus targeting form that promotes expression of UPR-responsive genes. The consequences of UPR activation are necessary for viral replication and pathogenesis. ATF, activating transcription factor; CHOP, C/EBP homologous protein; ER, endoplasmic reticulum; IRE1, inositol-requiring enzyme; PERK, protein kinase RNA like ER kinase; UPR, unfolded protein response.

Mentions: The ER contains an extensive network of tubules, sacs and cisternae, which extend from the cell plasma membrane through the cytoplasm and to the nuclear envelop through a continuous connected network (Refs 168, 169). The ER is the main sub-cellular compartment involved in proper folding of proteins and their maturation. Approximately one-third of the total proteins are synthesised in the ER. Many different perturbations can alter the function of the ER leading to unfolding or misfolding of proteins in the ER. This condition is referred to as ER stress (Refs 169, 170). The ER creates a series of adaptive mechanisms to prevent cell death complications and these together are referred to as the UPR (Refs 170, 171). The UPR can be involved in the secretory pathway leading to restoration of protein folding homeostasis. However, if there is too much stress on the ER, and the ER cannot cope with this stress, it will eventually lead to cell death (Ref. 172). The UPR also plays an important role in maintaining cellular homeostasis of specialised secretory cells such as pancreatic beta cells, salivary glands and plasma B cells (Ref. 170). It is becoming increasingly evident from animal models that UPR has several functions that are not directly linked to protein folding including inflammation, energy control and lipid and cholesterol metabolism (Ref. 170). The existence of UPR was first reported by Kozatsumi et al. more than 25 years ago (Ref. 173). They showed that glucose regulated proteins (GRPs) that are associated with the ER are up-regulated upon sensing the presence of unfolded or misfolded proteins in the ER (Ref. 173). While the mechanisms and signalling events behind it were not known at the time, today we have a much better understanding of the UPR and how these events are regulated in the ER at the molecular level. ER stress response signals are constantly monitored by three main classes of sensors. These include inositol requiring enzyme 1 alpha (IRE-1α) and IRE-1β, protein kinase RNA like ER kinase (PERK) and activating transcription factor 6 (ATF6; both α and β isoforms) (Fig. 5). In normal healthy cells these sensors are in an inactive state.Figure 5.


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 ER stress and virus replication. ER stress is enhanced in the viral infected cells and activates UPR proteins (e.g. PERK, ATF6, and IRE1). Activated PERK leads to induce ATF4 via phosphorylation of eIF2α, causing attenuation of translation and inducing genes encoding CHOP. Upon IRE1 activation, TRAF2 and sXBPmRNA1 splicing are initiated in the cytoplasm, subsequently leading to activation of UPR target genes. The degradation of ATF6 is increased through recruitment of ATF6, a UPR sensor. ATF6 translocates to the Golgi and is cleaved to a nucleus targeting form that promotes expression of UPR-responsive genes. The consequences of UPR activation are necessary for viral replication and pathogenesis. ATF, activating transcription factor; CHOP, C/EBP homologous protein; ER, endoplasmic reticulum; IRE1, inositol-requiring enzyme; PERK, protein kinase RNA like ER kinase; UPR, unfolded protein response.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig05: Graphic representation of ER stress and virus replication. ER stress is enhanced in the viral infected cells and activates UPR proteins (e.g. PERK, ATF6, and IRE1). Activated PERK leads to induce ATF4 via phosphorylation of eIF2α, causing attenuation of translation and inducing genes encoding CHOP. Upon IRE1 activation, TRAF2 and sXBPmRNA1 splicing are initiated in the cytoplasm, subsequently leading to activation of UPR target genes. The degradation of ATF6 is increased through recruitment of ATF6, a UPR sensor. ATF6 translocates to the Golgi and is cleaved to a nucleus targeting form that promotes expression of UPR-responsive genes. The consequences of UPR activation are necessary for viral replication and pathogenesis. ATF, activating transcription factor; CHOP, C/EBP homologous protein; ER, endoplasmic reticulum; IRE1, inositol-requiring enzyme; PERK, protein kinase RNA like ER kinase; UPR, unfolded protein response.
Mentions: The ER contains an extensive network of tubules, sacs and cisternae, which extend from the cell plasma membrane through the cytoplasm and to the nuclear envelop through a continuous connected network (Refs 168, 169). The ER is the main sub-cellular compartment involved in proper folding of proteins and their maturation. Approximately one-third of the total proteins are synthesised in the ER. Many different perturbations can alter the function of the ER leading to unfolding or misfolding of proteins in the ER. This condition is referred to as ER stress (Refs 169, 170). The ER creates a series of adaptive mechanisms to prevent cell death complications and these together are referred to as the UPR (Refs 170, 171). The UPR can be involved in the secretory pathway leading to restoration of protein folding homeostasis. However, if there is too much stress on the ER, and the ER cannot cope with this stress, it will eventually lead to cell death (Ref. 172). The UPR also plays an important role in maintaining cellular homeostasis of specialised secretory cells such as pancreatic beta cells, salivary glands and plasma B cells (Ref. 170). It is becoming increasingly evident from animal models that UPR has several functions that are not directly linked to protein folding including inflammation, energy control and lipid and cholesterol metabolism (Ref. 170). The existence of UPR was first reported by Kozatsumi et al. more than 25 years ago (Ref. 173). They showed that glucose regulated proteins (GRPs) that are associated with the ER are up-regulated upon sensing the presence of unfolded or misfolded proteins in the ER (Ref. 173). While the mechanisms and signalling events behind it were not known at the time, today we have a much better understanding of the UPR and how these events are regulated in the ER at the molecular level. ER stress response signals are constantly monitored by three main classes of sensors. These include inositol requiring enzyme 1 alpha (IRE-1α) and IRE-1β, protein kinase RNA like ER kinase (PERK) and activating transcription factor 6 (ATF6; both α and β isoforms) (Fig. 5). In normal healthy cells these sensors are in an inactive state.Figure 5.

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