West Nile virus capsid protein inhibits autophagy by AMP-activated protein kinase degradation in neurological disease development

Kobayashi, Shintaro; Yoshii, Kentaro; Phongphaew, Wallaya; Muto, Memi; Hirano, Michiyo; Orba, Yasuko; Sawa, Hirofumi; Kariwa, Hiroaki

doi:10.1371/journal.ppat.1008238

Cited by 30 publications

(30 citation statements)

References 52 publications

(71 reference statements)

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“…The C protein plays an important role in virus replication through its interaction with E3 ligases such as HDM2 [ 80 ]. The C protein also plays a role in the degradation of its binding proteins through the proteasome pathway [ 81 , 82 , 83 ]. The key role of the C protein is in nucleocapsid assembly; thus, the C protein shelters the viral genetic material (RNA).…”

Section: Virus Biologymentioning

confidence: 99%

West Nile Virus: An Update on Pathobiology, Epidemiology, Diagnostics, Control and “One Health” Implications

et al. 2020

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West Nile virus (WNV) is an important zoonotic flavivirus responsible for mild fever to severe, lethal neuroinvasive disease in humans, horses, birds, and other wildlife species. Since its discovery, WNV has caused multiple human and animal disease outbreaks in all continents, except Antarctica. Infections are associated with economic losses, mainly due to the cost of treatment of infected patients, control programmes, and loss of animals and animal products. The pathogenesis of WNV has been extensively investigated in natural hosts as well as in several animal models, including rodents, lagomorphs, birds, and reptiles. However, most of the proposed pathogenesis hypotheses remain contentious, and much remains to be elucidated. At the same time, the unavailability of specific antiviral treatment or effective and safe vaccines contribute to the perpetuation of the disease and regular occurrence of outbreaks in both endemic and non-endemic areas. Moreover, globalisation and climate change are also important drivers of the emergence and re-emergence of the virus and disease. Here, we give an update of the pathobiology, epidemiology, diagnostics, control, and “One Health” implications of WNV infection and disease.

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Section: Virus Biologymentioning

confidence: 99%

West Nile Virus: An Update on Pathobiology, Epidemiology, Diagnostics, Control and “One Health” Implications

et al. 2020

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“…AMPK-related autophagy is a mechanism utilized by many other viruses such as Epstein–Barr virus (EBV) [ 91 ], HIV [ 92 ], Newcastle disease virus (NDV)[ 93 ], porcine circovirus type 2 (PCV2) [ 94 , 95 ], avian reovirus (ARV)[ 90 ], influenza A [ 96 ], West Nile virus (WNV) [ 97 ], bluetongue virus (BTV) [ 98 , 99 , 100 ], duck enteritis virus (DEV) [ 101 , 102 ], rabies virus (RABV) [ 103 , 104 ] and swine fever virus (CSFV) [ 105 ].…”

Section: Interaction Between Viruses and Ampk Pathwaysmentioning

confidence: 99%

Multifaceted Role of AMPK in Viral Infections

Bhutta

Gallo²,

Borenstein

2021

Cells

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Viral pathogens often exploit host cell regulatory and signaling pathways to ensure an optimal environment for growth and survival. Several studies have suggested that 5′-adenosine monophosphate-activated protein kinase (AMPK), an intracellular serine/threonine kinase, plays a significant role in the modulation of infection. Traditionally, AMPK is a key energy regulator of cell growth and proliferation, host autophagy, stress responses, metabolic reprogramming, mitochondrial homeostasis, fatty acid β-oxidation and host immune function. In this review, we highlight the modulation of host AMPK by various viruses under physiological conditions. These intracellular pathogens trigger metabolic changes altering AMPK signaling activity that then facilitates or inhibits viral replication. Considering the COVID-19 pandemic, understanding the regulation of AMPK signaling following infection can shed light on the development of more effective therapeutic strategies against viral infectious diseases.

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“…The viral titer was measured as described previously 13 . Immunoprecipitation, immunoblotting, and lectin blotting. Cell lysates were prepared as described previously 34 . The lysates were precleared on SureBeads Protein G (Bio-Rad, Hercules, CA) for 30 min at 4 °C.…”

Section: Construction Of Plasmidsmentioning

confidence: 99%

“…The complexes were detected using horseradish peroxidase (HRP)-conjugated secondary antibodies or alkaline phosphatase-conjugated streptavidin (Jackson ImmunoResearch). Protein bands were visualised as described previously 34 .…”

Section: Construction Of Plasmidsmentioning

confidence: 99%

“…For immunohistochemical analysis, deparaffinised sections were subjected to antigen retrieval by trypsin digestion at 37 °C for 10 min for the WNV antigen and by heating in a pressure cooker in 0.01 M citrate buffer (pH 6.0) for CD3 or CD8, and were immunostained as described previously 33 . For quantification of CD3 or CD8-positive cells, the antigen-positive cells in the hippocampus were counted and calculated as described previously 34 . For detection of apoptotic cells, an in situ cell death detection kit (Roche) was used according to the manufacturer's instructions.…”

Section: Inoculation Of Mice With Wnvmentioning

confidence: 99%

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Amino acid 159 of the envelope protein affects viral replication and T-cell infiltration by West Nile virus in intracranial infection

Kobayashi

Kaneko

Kawakami

et al. 2020

Sci Rep

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West Nile virus (WNV) is an important cause of viral encephalitis in birds and animals, includinghumans. Amino acid 159 of the envelope (E) protein is reportedly implicated in the different levels of neurovirulence in mice infected with WNV NY99 or Eg101. We investigated the role of amino acid 159 of the E protein in the pathogenesis of WNV infection. We produced recombinant WNV with the structural proteins of the NY99 or Eg101 strain (NY-WT or EgCME-WT) and mutant viruses with substitutions of amino acid 159 of the E protein (NY-E-V159I or EgCME-E-I159V). The NY-WT and NY-E-V159I or EgCME-WT and EgCME-E-I159V titers in culture supernatant were similar. The mortality rate and viral titer in the brains of mice inoculated intraperitoneally with NY-WT or NY-E-V159I were also similar. In contrast, the mortality rate and viral titer in the brains of mice inoculated intracranially with EgCME-E-I159V were significantly higher than those of mice inoculated with EgCME-WT. The numbers of CD3positive and CD8-positive T cells were greater in brains inoculated with EgCME-E-I159V than in those inoculated with EgCME-WT. Therefore, amino acid 159 of the E protein modulates the pathogenicity of WNV by affecting viral replication and T-cell infiltration in the brain. Figure 4. Infiltration of T cells in mouse brains infected with recombinant WNV. C57BL/6 mice were inoculated intracranially with 10 pfu EgCME-WT or EgCME-E-I159V. (A) Images of haematoxylin and eosin-stained sections of the cerebral cortex, sections stained by TUNEL or immunostained for WNV antigen, CD3, or CD8 (n = 5). White arrowheads, degenerated neuronal cells; black arrowheads, TUNEL-positive cells, CD3-positive cells, or CD8-positive cells. Scale bar, 25 μm. (B) Number of CD3-or CD8-positive cells in the hippocampus (n = 5). Statistical significance was assessed by the two-tailed Student's t-test. *p < 0.05; **p < 0.01. (C) Relationship between CD3-positive T cells and WNV antigen-positive cells. Sections were stained with antibodies against CD3 (green) and WNV antigen (red). Nuclei were stained with DAPI (blue). White arrowheads indicate CD3-positive T cells adjacent to viral antigen-positive cells. Scale bar, 20 μm. (D) Expression levels of genes encoding immune factors in brains inoculated with EgCME-WT or EgCME-E-I159V. MethodsCells. Vero cells, obtained from the JCRB Cell Bank (JCRB0111), were cultured in an atmosphere containing 5% CO 2 at 37 °C in modified Eagles' medium (MEM; Wako, Osaka, Japan) supplemented with 10% heat-inactivated fetal bovine serum (FBS). SH-SY 5Y cells, obtained from the European Collection of Authenticated Cell Cultures (94030304), were cultured in an atmosphere containing 5% CO 2 at 37 °C in Dulbecco's MEM (DMEM)/ Nutrient Mixture F-12 Ham (Wako) supplemented with 10% heat-inactivated FBS. HEK-293T cells, kindly provided by Dr. Matsuura (Osaka University), were cultured in an atmosphere containing 5% CO 2 at 37 °C in high-glucose DMEM (Wako) supplemented with 10% heat-inactivated FBS.

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West Nile virus capsid protein inhibits autophagy by AMP-activated protein kinase degradation in neurological disease development

Cited by 30 publications

References 52 publications

West Nile Virus: An Update on Pathobiology, Epidemiology, Diagnostics, Control and “One Health” Implications

West Nile Virus: An Update on Pathobiology, Epidemiology, Diagnostics, Control and “One Health” Implications

Multifaceted Role of AMPK in Viral Infections

Amino acid 159 of the envelope protein affects viral replication and T-cell infiltration by West Nile virus in intracranial infection

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