Japanese Encephalitis Virus NS2B-3 Protein Complex Promotes Cell Apoptosis and Viral Particle Release by Down-Regulating the Expression of AXL

Xie, Shengda; Liang, Zhenjie; Yang, Xingmiao; Pan, Junhui; Yu, Du; Li, Tongtong; Cao, Rui

doi:10.1007/s12250-021-00442-3

Cited by 11 publications

(12 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The AXL protein, belonging to the PS receptor, also inhibits the release of JEV. JEV NS2B-3 protein complex promotes viral particle release by down-regulating the expression of AXL (42). In our study, A549 cells were infected with a pair of JEV strains differently expressing NS1’ protein at low MOI to reduce the influence of NS1’ protein in the supernatant.…”

Section: Discussionmentioning

confidence: 99%

Japanese Encephalitis Virus NS1’ Protein regulates the expression and distribution of TIM-1 to promote viral infection

Liang¹,

Xie²,

Pan³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Japanese encephalitis virus (JEV) is a mosquito-borne Flavivirus, which may cause severe encephalitis in humans, horses, and other animals. TIM-1 has been identified to be a receptor that promotes various viruses to enter into target cells in recent years. In the present study, we found that TIM-1 protein was significantly increased in A549 cells at the late stage of JEV infection, while the transcription levels of TIM-1 remained unaltered. Interestingly, we found that NS1’ protein plays a key role in increasing the expression of TIM-1 in cells infected with JEV. Further, we found that the NS1’ protein also efficiently regulates TIM-1 protein to distribute in the cytoplasm in JEV-infected cells, and the amount of TIM-1 protein located on the cell membrane was reduced instead. As a consequence, NS1’ protein antagonize TIM-1 mediated viral restriction for further viral infection and propagation in the late stage of infection. In molecular mechanism, the molecular weight of TIM-1 increased a bit in the present of NS1’. Expression of NEU1 down-regulated TIM-1 expression and oseltamivir treatment increased the expression of TIM-1. Therefore, our data indicated that JEV NS1’ protein facilitated the sialylation modification of TIM-1 to up-regulate the level of TIM-1 expression and regulate its distribution. Collectively, our study revealed that JEV NS1’ protein regulates the expression and distribution of TIM-1 by facilitating its sialylation to antagonize TIM-1-mediated JEV restriction for further infection. Understanding the functional interplays between TIM-1 and NS1’ proteins will offer new insights into virus-host interaction.

show abstract

Section: Discussionmentioning

confidence: 99%

Japanese Encephalitis Virus NS1’ Protein regulates the expression and distribution of TIM-1 to promote viral infection

Liang¹,

Xie²,

Pan³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…PMs were isolated as previously described ( 49 ), 4-week-old ICR mice were euthanized and disinfected with 75% ethanol, followed by intraperitoneal injection with 5 mL DMEM. After 5 min of peritoneal massage and 10 min of incubation, PMs were collected from the peritoneal cavity and centrifuged at 400 × g for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Japanese Encephalitis Virus (JEV) NS1′ Enhances the Viral Infection of Dendritic Cells (DCs) and Macrophages in Pig Tonsils

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…The helicase and NTPase domain at the C-terminal end of NS is required for negative supercoiling of the dsRNA intermediate during JEV replication and transcription [ 71 , 72 ]. A recent study by Xie et al showed that the NS2B-NS3 protein complex induces cell apoptosis by degrading the AXL membrane protein through the ubiquitin-proteasome pathway [ 73 ]. Therefore, NS2B and NS3 are suitable therapeutic targets, as they play a central role in JEV replication and post-translational processing of the polyprotein.…”

Section: Jev Structure and Genome Organisationmentioning

confidence: 99%

“…The C-terminal ‘2K’ fragment of NS4A translocates the NS4B protein into the ER lumen by acting as a signal sequence [ 112 ]. NS5 is the most conserved and the largest protein (~100 kDa) in all flaviviruses, and it interacts strongly with NS3 and other NSPs as well as the genomic RNA in the RC [ 73 – 75 ]. The N-terminal domain (~30 kDa) of NS5 exhibits methyltransferase activity and is responsible for the addition of a methylated cap to the viral RNA at 5′ end [ 76 , 77 ].…”

Section: Jev Life Cyclementioning

confidence: 99%

Molecular pathogenesis of Japanese encephalitis and possible therapeutic strategies

et al. 2022

View full text Add to dashboard Cite

Japanese encephalitis virus (JEV), a single-stranded, enveloped RNA virus, is a health concern across Asian countries, associated with severe neurological disorders, especially in children. Primarily, pigs, bats, and birds are the natural hosts for JEV, but humans are infected incidentally. JEV requires a few host proteins for its entry and replication inside the mammalian host cell. The endoplasmic reticulum (ER) plays a significant role in JEV genome replication and assembly. During this process, the ER undergoes stress due to its remodelling and accumulation of viral particles and unfolded proteins, leading to an unfolded protein response (UPR). Here, we review the overall strategy used by JEV to infect the host cell and various cytopathic effects caused by JEV infection. We also highlight the role of JEV structural proteins (SPs) and non-structural proteins (NSPs) at various stages of the JEV life cycle that are involved in up- and downregulation of different host proteins and are potentially relevant for developing efficient therapeutic drugs. Graphical abstract

show abstract

Japanese Encephalitis Virus NS2B-3 Protein Complex Promotes Cell Apoptosis and Viral Particle Release by Down-Regulating the Expression of AXL

Cited by 11 publications

References 57 publications

Japanese Encephalitis Virus NS1’ Protein regulates the expression and distribution of TIM-1 to promote viral infection

Japanese Encephalitis Virus NS1’ Protein regulates the expression and distribution of TIM-1 to promote viral infection

Japanese Encephalitis Virus (JEV) NS1′ Enhances the Viral Infection of Dendritic Cells (DCs) and Macrophages in Pig Tonsils

Molecular pathogenesis of Japanese encephalitis and possible therapeutic strategies

Contact Info

Product

Resources

About