Regulation of autophagy, glucose uptake, and glycolysis under dengue virus infection

Lee, Ying‐Ray; Wu, Shan-Ying; Chen, Ruei Yi; Lin, Yee Shin; Yeh, Trai Ming; Liu, Hsiao Sheng

doi:10.1002/kjm2.12271

Cited by 22 publications

(22 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We reveal that DENV2 infection increased autophagic activity, glucose uptake, protein levels of glucose transporter‐1, glycolysis rate‐limiting enzyme hexokinase‐2 (HK2), and viral replication both in vitro and in vivo. We further confirmed that DENV‐induced autophagy induces lactate pathway‐independent glycolysis and viral replication 63 . Others reported that DENV infection triggers the release of autophagy‐related vesicles and the infection of other cells as well as the evasion of immune system surveillance 64 .…”

Section: Diseases Related To Aberrant Metabolism and Autophagysupporting

confidence: 80%

Autophagy and metabolism

Lin

Chu

Liu

2020

The Kaohsiung J of Med Scie

Self Cite

View full text Add to dashboard Cite

Metabolism consists of diverse life‐sustaining chemical reactions in living organisms. Autophagy is a highly conservative process that responds to various internal and external stresses. Both processes utilize surrounding resources to provide energy and nutrients for the cell. Autophagy progression may proceed to the degradative or secretory pathway determined by Rab family proteins. The former is a degradative and lysosome‐dependent catabolic process that produces energy and provides nutrients for the synthesis of essential proteins. The degradative pathway also balances the energy source of the cell and regulates tissue homeostasis. The latter is a newly discovered pathway in which the autophagosome is fused with the plasma membrane. Secretory autophagy participates in diverse functions and diseases ranging from the spread of viral particles to cancer and neurodegenerative diseases. Aberrant metabolism in the body causes various metabolic syndromes. This review explores the relationships among autophagy, metabolism, and related diseases.

show abstract

Section: Diseases Related To Aberrant Metabolism and Autophagysupporting

confidence: 80%

Autophagy and metabolism

Lin

Chu

Liu

2020

The Kaohsiung J of Med Scie

Self Cite

View full text Add to dashboard Cite

show abstract

“…We previously reported that DENV2 and EV71 infection-induced autophagy promotes viral replication and pathogenesis [17][18][19][20][21][22]. DENV2 infection activates the autophagy machinery to form autophagosomes.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, DENV infection induced-autophagy also regulates cellular mechanisms, such as lipid metabolism and DENV2 induced-autophagy selectively engulfs the lipid droplets followed by the release of free fatty acids, which are converted to β-oxidation to produce ATP and promote DENV replication [24]. Furthermore, we previously reported that DENV2-induced glycolysis and ER stress increases autophagy activity, viral replication and pathogenesis through different signaling pathways both in vitro and in vivo [17,18]. Moreover, DENV NS4A protein can also induce autophagy through the activation of unfolded protein response (UPR) [25].…”

Section: Introductionmentioning

confidence: 99%

The Autophagosomes Containing Dengue Virus Proteins and Full-Length Genomic RNA Are Infectious

Chen

Lee

et al. 2021

Viruses

View full text Add to dashboard Cite

Autophagic machinery is involved in selective and non-selective recruitment as well as degradation or exocytosis of cargoes, including pathogens. Dengue virus (DENV) infectioninduces autophagy that enhances virus replication and vesicle release to evade immune systemsurveillance. This study reveals that DENV2 induces autophagy in lung and liver cancer cells andshowed that DENV2 capsid, envelope, NS1, NS3, NS4B and host cell proinflammatory high mobilitygroup box 1 (HMGB1) proteins associated with autophagosomes which were purified by gradientcentrifugation. Capsid, NS1 and NS3 proteins showing high colocalization with LC3 protein in thecytoplasm of the infected cells were detected in the purified double-membrane autophagosome byimmunogold labeling under transmission electron microscopy. In DENV infected cells, the levels ofcapsid, envelope, NS1 and HMGB1 proteins are not significantly changed compared to the dramaticaccumulation of LC3-II and p62/SQSTM1 proteins when autophagic degradation was blocked bychloroquine, indicating that these proteins are not regulated by autophagic degradation machinery.We further demonstrated that purified autophagosomes were infectious when co-cultured withuninfected cells. Notably, these infectious autophagosomes contain DENV2 proteins, negativestrandand full-length genomic RNAs, but no viral particles. It is possible that the infectivity ofthe autophagosome originates from the full-length DENV RNA. Moreover, we reveal that DENV2promotes HMGB1 exocytosis partially through secretory autophagy. In conclusion, we are the firstto report that DENV2-induced double-membrane autophagosomes containing viral proteins andfull-length RNAs are infectious and not undergoing autophagic degradation. Our novel findingwarrants further validation of whether these intracellular vesicles undergo exocytosis to becomeinfectious autophagic vesicles.

show abstract

“…In this study, we identified the intranasal transmission of DENV under experimental conditions for the first time to facilitate a better understanding of non-vector-borne disease outbreaks in DENV endemic areas. To determine whether DENV can infect experimental mice through the intranasal route, BALB/c suckling mice, which are widely used in DENV research [ 22 , 23 ], and adult IFN-α/β receptor-deficient mice (A6 mice), which are susceptible to DENV [ 24 ], were exposed to dengue virus serotype 2 (DENV-2) through intranasal inoculation.…”

Section: Introductionmentioning

confidence: 99%

Effective Infection with Dengue Virus in Experimental Neonate and Adult Mice through the Intranasal Route

Qiu

Zhao

Zhang

et al. 2022

Viruses

View full text Add to dashboard Cite

Dengue virus, the causative agent of dengue fever, life-threatening hemorrhagic fever, and shock syndrome, is mainly transmitted to humans through mosquito vectors. It can also be transmitted through atypical routes, including needle stick injury, vertical transmission, blood transfusion, and organ transplantation. In addition, sporadic cases which have no clear infectious causes have raised the respiratory exposure concerns, and the risks remain unclear. Here, we analyze the respiratory infectivity of the dengue virus in BALB/c suckling and adult immunodeficient mice by the intranasal inoculation of dengue virus serotype 2. The infected mice presented with clinical symptoms, including excitement, emaciation, malaise, and death. Viremia was detected for 3 days post inoculation. Histopathological changes were observed in the brain, liver, and spleen. The virus showed evident brain tropism post inoculation and viral loads peaked at 7 days post inoculation. Furthermore, the virus was isolated from the infected mice; the sequence homology between the origin and isolates was 99.99%. Similar results were observed in adult IFN-α/β receptor-deficient mice. Overall, dengue virus can infect suckling mice and adult immune-deficient mice via the nasal route. This study broadens our perception of atypical dengue transmission routes and provides evidence of nasal transmission of dengue virus in the absence of mosquito vectors.

show abstract

Regulation of autophagy, glucose uptake, and glycolysis under dengue virus infection

Cited by 22 publications

References 37 publications

Autophagy and metabolism

Autophagy and metabolism

The Autophagosomes Containing Dengue Virus Proteins and Full-Length Genomic RNA Are Infectious

Effective Infection with Dengue Virus in Experimental Neonate and Adult Mice through the Intranasal Route

Contact Info

Product

Resources

About