Autophagy in Zika Virus Infection: A Possible Therapeutic Target to Counteract Viral Replication

Gratton, Rossella; Agrelli, Almerinda; Tricarico, Paola Maura; Brandão, Lucas André Cavalcanti; Crovella, Sérgio

doi:10.3390/ijms20051048

Cited by 39 publications

(35 citation statements)

References 121 publications

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“…In addition, CQ also has some antiviral activities by autophagyindependent pathways. CQ is weak base, and meddles in protein processing, and degradation by alkalifying the acidic organelles like Golgi vesicles, endosomes, lysosomes (Gratton et al, 2019). And the low pH is essential for the entry, the viral RNA release, and the exit of flaviviruses, like ZIKV, DENV, HCV, and others (Tscherne et al, 2006;Sánchez-San Martín et al, 2009;Zheng et al, 2014;Persaud et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Autophagy Is a Potential Therapeutic Target Against Duck Tembusu Virus Infection in vivo

Pan

Cheng

et al. 2020

Front. Cell. Infect. Microbiol.

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Duck tembusu virus (DTMUV) is newly emerged in poultry and causes great losses to the breeding industry in China and neighboring countries. Effective antiviral strategies are still being studied. Autophagy is a cellular degradative pathway, and our lab's previous data show that autophagy promotes DTMUV replication in vitro. To study the role of autophagy further in vivo, we utilized ducks as the animal model to investigate the autophagy responses in DTMUV-targeted tissues. And also, we utilized autophagy regulators, including Rapamycin (Rapa) as the autophagy enhancer, 3-Methyladenine (3-MA) and Chloroquine (CQ) as the autophagy inhibitors, to adjust the host autophagic levels and then study the effects of autophagy on tissue damages and virus replication. As a result, we first found DTMUV infection trigged autophagy and autophagy regulator treatments regulated autophagy levels successfully in duck spleens and brains. Next, we found that autophagy inhibitors inhibited DTMUV replication and alleviated DTMUV-induced pathological symptoms, whereas the autophagy inducer treatment led to the opposite effects. And we also found that autophagic regulation was correlated with the expression of innate immune genes, including pattern recognition receptors, type I interferons, and cytokines, and caused different effects in different tissues. In summary, we demonstrated that autophagy facilitated DTMUV replication, aggravated the developments of pathological symptoms and possibly counteracts the host's innate immunity response in vivo.

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Section: Discussionmentioning

confidence: 99%

Autophagy Is a Potential Therapeutic Target Against Duck Tembusu Virus Infection in vivo

Pan

Cheng

et al. 2020

Front. Cell. Infect. Microbiol.

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“…The induction of autophagy by ZIKV appears to be linked to the activation of AMPK, while DENV induces autophagy by activation of VPS34 (98). USP10 and USP13 are needed to reverse ubiquitination and subsequently degradation of the Beclin1-VPS34-ATG14 complex.…”

Section: Therapeutic Strategies Aiming To Inhibit Autophagy To Block mentioning

confidence: 99%

Targeting Autophagy in Innate Immune Cells: Angel or Demon During Infection and Vaccination?

Tao

Drexler

2020

Front. Immunol.

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Innate immune cells are the "doorkeepers" in the immune system and are important for the initiation of protective vaccine responses against infection. Being an essential regulatory component of the immune system in these cells, autophagy not only mediates pathogen clearance and cytokine production, but also balances the immune response by preventing harmful overreaction. Interestingly, recent literature indicates that autophagy is positively or negatively regulating the innate immune response in a cell type-specific manner. Moreover, autophagy serves as a bridge between innate and adaptive immunity. It is involved in antigen presentation by delivering pathogen compounds to B and T cells, which is important for effective immune protection. Upon infection, autophagy can also be hijacked by some pathogens for replication or evade host immune responses. As a result, autophagy seems like a double-edged sword to the immune response, strongly depending on the cell types involved and infection models used. In this review, the dual role of autophagy in regulating the immune system will be highlighted in various infection models with particular focus on dendritic cells, monocytes/macrophages and neutrophils. Targeting autophagy in these cells as for therapeutic application or prophylactic vaccination will be discussed considering both roles of autophagy, the "angel" enhancing innate immune responses, antigen presentation, pathogen clearance and dampening inflammation or the "demon" enabling viral replication and degrading innate immune components. A better understanding of this dual potential will help to utilize autophagy in innate immune cells in order to optimize vaccines or treatments against infectious diseases.

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“…Therefore, the possibility of placental colonization by ZIKV and subsequent fetal infection could occur by secretory autophagy [ 105 , 106 , 107 ] and through exosomes, since flavivirus exploits this pathway to spread infection [ 10 , 14 , 15 , 16 ]. However, the transmission of ZIKV through exosomes by the placenta has not been reported so far.…”

Section: Exosomes As a Transplacental Infection Route Of Zikv: A Hmentioning

confidence: 99%

The Regulation of Flavivirus Infection by Hijacking Exosome-Mediated Cell–Cell Communication: New Insights on Virus–Host Interactions

Reyes-Ruiz

Osuna-Ramos

Jesús-González

et al. 2020

Viruses

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The arthropod-borne flaviviruses are important human pathogens, and a deeper understanding of the virus–host cell interaction is required to identify cellular targets that can be used as therapeutic candidates. It is well reported that the flaviviruses hijack several cellular functions, such as exosome-mediated cell communication during infection, which is modulated by the delivery of the exosomal cargo of pro- or antiviral molecules to the receiving host cells. Therefore, to study the role of exosomes during flavivirus infections is essential, not only to understand its relevance in virus–host interaction, but also to identify molecular factors that may contribute to the development of new strategies to block these viral infections. This review explores the implications of exosomes in flavivirus dissemination and transmission from the vector to human host cells, as well as their involvement in the host immune response. The hypothesis about exosomes as a transplacental infection route of ZIKV and the paradox effect or the dual role of exosomes released during flavivirus infection are also discussed here. Although several studies have been performed in order to identify and characterize cellular and viral molecules released in exosomes, it is not clear how all of these components participate in viral pathogenesis. Further studies will determine the balance between protective and harmful exosomes secreted by flavivirus infected cells, the characteristics and components that distinguish them both, and how they could be a factor that determines the infection outcome.

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Autophagy in Zika Virus Infection: A Possible Therapeutic Target to Counteract Viral Replication

Cited by 39 publications

References 121 publications

Autophagy Is a Potential Therapeutic Target Against Duck Tembusu Virus Infection in vivo

Autophagy Is a Potential Therapeutic Target Against Duck Tembusu Virus Infection in vivo

Targeting Autophagy in Innate Immune Cells: Angel or Demon During Infection and Vaccination?

The Regulation of Flavivirus Infection by Hijacking Exosome-Mediated Cell–Cell Communication: New Insights on Virus–Host Interactions

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