2017
DOI: 10.1080/15548627.2016.1265192
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Dengue and Zika viruses subvert reticulophagy by NS2B3-mediated cleavage of FAM134B

Abstract: The endoplasmic reticulum (ER) is exploited by several diverse viruses during their infectious life cycles. Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), utilize the ER as a source of membranes to establish their replication organelles and to facilitate their assembly and eventual maturation along the secretory pathway. To maintain normal homeostasis, host cells have evolved highly efficient processes to dynamically regulate the ER, such as through reticulophagy, a selective form of autoph… Show more

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Cited by 167 publications
(188 citation statements)
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“…The upregulation of Fam134b in AT‐1 sTg mice was also observed when we analyzed mRNA (Figure 5f) and protein levels (Figure 5g,h). Fam134b has recently emerged as a novel regulator of ER‐autophagy, and levels of Fam134b seem to reflect intrinsic dynamics of reticulophagy (Khaminets et al, 2015; Lennemann & Coyne, 2017; Mochida et al, 2015; Nakatogawa & Mochida, 2015; Rubinsztein, 2015). Therefore, increased steady‐state levels of Fam134b in AT‐1 sTg mice (Figure 5d–h) are consistent with the observed ER expansion (Figure 5c and Supporting Information Figure S3d), as they might reflect reduced turnover of the ER‐associated Fam134b protein as well as an attempt of the cell to restore reticulophagy by activating Fam134b translation.…”
Section: Resultsmentioning
confidence: 99%
“…The upregulation of Fam134b in AT‐1 sTg mice was also observed when we analyzed mRNA (Figure 5f) and protein levels (Figure 5g,h). Fam134b has recently emerged as a novel regulator of ER‐autophagy, and levels of Fam134b seem to reflect intrinsic dynamics of reticulophagy (Khaminets et al, 2015; Lennemann & Coyne, 2017; Mochida et al, 2015; Nakatogawa & Mochida, 2015; Rubinsztein, 2015). Therefore, increased steady‐state levels of Fam134b in AT‐1 sTg mice (Figure 5d–h) are consistent with the observed ER expansion (Figure 5c and Supporting Information Figure S3d), as they might reflect reduced turnover of the ER‐associated Fam134b protein as well as an attempt of the cell to restore reticulophagy by activating Fam134b translation.…”
Section: Resultsmentioning
confidence: 99%
“…An impairment of ER‐phagy or inefficiency in the autophagosomal–lysosomal system is associated with bacterial and viral infection or with conformational diseases, including liver, muscle and neurodegenerative diseases or ageing conditions . In these conditions, misfolded proteins are not efficiently removed from the ER, thus leading to aggregate formation, propagation with disruption of cellular fitness and damage of multiple tissues.…”
Section: Defective Erlad In Human Diseasesmentioning
confidence: 99%
“…It is now believed that DENV benefits from a combination of increased autophagy-mediated lipid metabolism, resulting in an energetically favorable environment and efficient processing of mature virions (Figure 1) [17,29]. Simultaneously, autophagy is counteracting the effects of infection; the selective autophagy adapter protein, p62, targets DENV proteins for degradation and reticulophagy actively removes ER damaged by DENV replication complexes (Figure 1) [24,30]. It is still unclear if this model of autophagy-flavivirus interactions is applicable to other flaviviruses.…”
Section: Mammalian Autophagy and Arbovirusesmentioning
confidence: 99%
“…Some evidence with other flaviviruses supports this model. For instance, like DENV, ZIKV benefits from autophagy while at the same time actively resisting reticulophagy [30]. Conversely, other evidence suggests that each flavivirus has a unique relationship with autophagy.…”
Section: Mammalian Autophagy and Arbovirusesmentioning
confidence: 99%