Polarization of Type 1 Macrophages Is Associated with the Severity of Viral Encephalitis Caused by Japanese Encephalitis Virus and Dengue Virus

Infection with flaviviruses causes mild to severe diseases, including viral hemorrhagic fever, vascular shock syndrome, and viral encephalitis. Several animal models explore the pathogenesis of viral encephalitis, as shown by neuron destruction due to neurotoxicity after viral infection. While neuronal cells are injuries caused by inflammatory cytokine production following microglial/macrophage activation, the blockade of inflammatory cytokines can reduce neurotoxicity to improve the survival rate. This study investigated the involvement of macrophage phenotypes in facilitating CNS inflammation and neurotoxicity during flavivirus infection, including the Japanese encephalitis virus, dengue virus (DENV), and Zika virus. Mice infected with different flaviviruses presented encephalitis-like symptoms, including limbic seizure and paralysis. Histology indicated that brain lesions were identified in the hippocampus and surrounded by mononuclear cells. In those regions, both the infiltrated macrophages and resident microglia were significantly increased. RNA-seq analysis showed the gene profile shifting toward type 1 macrophage (M1) polarization, while M1 markers validated this phenomenon. Pharmacologically blocking C-C chemokine receptor 2 and tumor necrosis factor-α partly retarded DENV-induced M1 polarization. In summary, flavivirus infection, such as JEV and DENV, promoted type 1 macrophage polarization in the brain associated with encephalitic severity.

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mosGCTL-7, a C-Type Lectin Protein, Mediates Japanese Encephalitis Virus Infection in Mosquitoes

Journal of Virology ◽

10.1128/jvi.01348-16 ◽

2017 ◽

Vol 91 (10) ◽

Cited By ~ 13

Author(s):

Ke Liu ◽

Yingjuan Qian ◽

Yong-Sam Jung ◽

Bin Zhou ◽

Ruibing Cao ◽

...

Keyword(s):

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Envelope Protein ◽

Viral Encephalitis ◽

Encephalitis Virus ◽

Content Type ◽

Flavivirus Infection ◽

New Strategies

ABSTRACT Japanese encephalitis virus (JEV) is an arthropod-borne flavivirus prevalent in Asia and the Western Pacific and is the leading cause of viral encephalitis. JEV is maintained in a transmission cycle between mosquitoes and vertebrate hosts, but the molecular mechanisms by which the mosquito vector participates in transmission are unclear. We investigated the expression of all C-type lectins during JEV infection in Aedes aegypti. The C-type lectin mosquito galactose-specific C-type lectin 7 (mosGCTL-7) (VectorBase accession no. AAEL002524) was significantly upregulated by JEV infection and facilitated infection in vivo and in vitro. mosGCTL-7 bound to the N-glycan at N154 on the JEV envelope protein. This recognition of viral N-glycan by mosGCTL-7 is required for JEV infection, and we found that this interaction was Ca2+ dependent. After mosGCTL-7 bound to the glycan, mosPTP-1 bound to mosGCTL-7, promoting JEV entry. The viral burden in vivo and in vitro was significantly decreased by mosPTP-1 double-stranded RNA (dsRNA) treatment, and infection was abolished by anti-mosGCTL-7 antibodies. Our results indicate that the mosGCTL-7/mosPTP-1 pathway plays a key role in JEV infection in mosquitoes. An improved understanding of the mechanisms underlying flavivirus infection in mosquitoes will provide further opportunities for developing new strategies to control viral dissemination in nature. IMPORTANCE Japanese encephalitis virus is a mosquito-borne flavivirus and is the primary cause of viral encephalitis in the Asia-Pacific region. Twenty-four countries in the WHO Southeast Asia and Western Pacific regions have endemic JEV transmission, which exposes >3 billion people to the risks of infection, although JEV primarily affects children. C-type lectins are host factors that play a role in flavivirus infection in humans, swine, and other mammals. In this study, we investigated C-type lectin functions in JEV-infected Aedes aegypti and Culex pipiens pallens mosquitoes and cultured cells. JEV infection changed the expression of almost all C-type lectins in vivo and in vitro, and mosGCTL-7 bound to the JEV envelope protein via an N-glycan at N154. Cell surface mosPTP-1 interacted with the mosGCTL-7–JEV complex to facilitate virus infection in vivo and in vitro. Our findings provide further opportunities for developing new strategies to control arbovirus dissemination in nature.

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Dengue virus and Japanese encephalitis virus infection of the central nervous system share similar profiles of cytokine accumulation in cerebrospinal fluid

Central European Journal of Immunology ◽

10.5114/ceji.2017.69366 ◽

2017 ◽

Vol 2 ◽

pp. 218-222 ◽

Cited By ~ 4

Author(s):

Haipeng Li ◽

Yuanyuan Li ◽

Bo Wen ◽

Jian Zhang ◽

Chengwu Wang ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Virus Infection ◽

Dengue Virus ◽

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Encephalitis Virus ◽

Japanese Encephalitis Virus Infection ◽

The Central Nervous System

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Human MxB Inhibits the Replication of Hepatitis C Virus

Journal of Virology ◽

10.1128/jvi.01285-18 ◽

2018 ◽

Vol 93 (1) ◽

Cited By ~ 7

Author(s):

Dong-Rong Yi ◽

Ni An ◽

Zhen-Long Liu ◽

Feng-Wen Xu ◽

Kavita Raniga ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Dengue Virus ◽

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Rna Replication ◽

Encephalitis Virus ◽

Common Mechanism ◽

Type I ◽

Dependent Manner

ABSTRACTType I interferon (IFN) inhibits viruses by inducing the expression of antiviral proteins. The IFN-induced myxovirus resistance B (MxB) protein has been reported to inhibit a limited number of viruses, including HIV-1 and herpesviruses, but its antiviral coverage remains to be explored further. Here we show that MxB interferes with RNA replication of hepatitis C virus (HCV) and significantly inhibits viral replication in a cyclophilin A (CypA)-dependent manner. Our data further show that MxB interacts with the HCV protein NS5A, thereby impairing NS5A interaction with CypA and NS5A localization to the endoplasmic reticulum, two events essential for HCV RNA replication. Interestingly, we found that MxB significantly inhibits two additional CypA-dependent viruses of theFlaviviridaefamily, namely, Japanese encephalitis virus and dengue virus, suggesting a potential link between virus dependence on CypA and virus susceptibility to MxB inhibition. Collectively, these data have identified MxB as a key factor behind IFN-mediated suppression of HCV infection, and they suggest that other CypA-dependent viruses may also be subjected to MxB restriction.IMPORTANCEViruses of theFlaviviridaefamily cause major illness and death around the world and thus pose a great threat to human health. Here we show that IFN-inducible MxB restricts several members of theFlaviviridae, including HCV, Japanese encephalitis virus, and dengue virus. This finding not only suggests an active role of MxB in combating these major pathogenic human viruses but also significantly expands the antiviral spectrum of MxB. Our study further strengthens the link between virus dependence on CypA and susceptibility to MxB restriction and also suggests that MxB may employ a common mechanism to inhibit different viruses. Elucidating the antiviral functions of MxB advances our understanding of IFN-mediated host antiviral defense and may open new avenues to the development of novel antiviral therapeutics.

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A dataset of distribution and diversity of mosquito-associated viruses and their mosquito vectors in China

Scientific Data ◽

10.1038/s41597-020-00687-9 ◽

2020 ◽

Vol 7 (1) ◽

Author(s):

Evans Atoni ◽

Lu Zhao ◽

Cheng Hu ◽

Nanjie Ren ◽

Xiaoyu Wang ◽

...

Keyword(s):

Dengue Virus ◽

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Mosquito Species ◽

Encephalitis Virus ◽

Health Concern ◽

Mosquito Vector ◽

Mosquito Vectors ◽

Culex Flavivirus ◽

Conference Papers

Abstract Mosquito-borne viruses such as Zika virus, Japanese Encephalitis virus and Dengue virus present an increasing global health concern. However, in-depth knowledge of the distribution and diversity of mosquito-associated viruses and their related vectors remains limited, especially for China. To promote their understanding, we present the first comprehensive dataset of the distribution and diversity of these viruses and their related vectors in China (including Taiwan, Hong Kong and Macau). Data was drawn from peer-reviewed journal articles, conference papers and thesis publications in both English and Chinese. Geographical data on mosquito-associated viruses’ occurrence and related mosquito vector species was extracted, and quality-control processes employed. This dataset contains 2,428 accounts of mosquito-associated viruses’ and mosquito species geo-referenced occurrences at various administrative levels in China. The prevalent mosquito-associated virus includes Japanese encephalitis virus, Dengue virus, Banna virus and Culex flavivirus, whereas the abundant mosquito vectors are Culex tritaeryohynchus, Aedes albopictus and Culex pipiens pallens. This geographical dataset delivers a distribution and diversity outline of mosquito-associated viruses in China, and also applicable in various spatial and risk-assessment analysis.

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Concurrent dengue virus and Japanese encephalitis virus infection

Infection ◽

10.1007/s15010-012-0311-0 ◽

2012 ◽

Vol 41 (2) ◽

pp. 589-589 ◽

Cited By ~ 1

Author(s):

B. Joob ◽

V. Wiwanitkit

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Encephalitis Virus ◽

Japanese Encephalitis Virus Infection

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Discordant Activity of Kaempferol Towards Dengue Virus and Japanese Encephalitis Virus

Molecules ◽

10.3390/molecules25051246 ◽

2020 ◽

Vol 25 (5) ◽

pp. 1246

Author(s):

Chit Care ◽

Wannapa Sornjai ◽

Janejira Jaratsittisin ◽

Atitaya Hitakarun ◽

Nitwara Wikan ◽

...

Keyword(s):

Dengue Virus ◽

Protein Expression ◽

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Denv Infection ◽

Significant Inhibition ◽

Encephalitis Virus ◽

Host Protein ◽

Cell Protein ◽

Infected Cells

Kaempferol, a plant-derived flavonoid, has been reported to have activity against Japanese encephalitis virus (JEV) in BHK-21 cells. To determine the broader utility of this compound, we initially evaluated the activity of kaempferol against JEV and dengue virus (DENV) in HEK293T/17 cells. Results showed no significant antiviral activity against either virus. We subsequently investigated the activity of kaempferol against both JEV and DENV in BHK-21 cells. Results showed a significant inhibition of JEV infection but, surprisingly, a significant enhancement of DENV infection. The effect of kaempferol on both host protein expression and transcription was investigated and both transcriptional and translational inhibitory effects were observed, although a more marked effect was observed on host cell protein expression. Markedly, while GRP78 was increased in DENV infected cells treated with kaempferol, it was not increased in JEV infected cells treated with kaempferol. These results show that cellular alteration induced by one compound can have opposite effects on viruses from the same family, suggesting the presence of distinct replication strategies for these two viruses.

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