scholarly journals Evaluation of the antiviral activity of orlistat (tetrahydrolipstatin) against dengue virus, Japanese encephalitis virus, Zika virus and chikungunya virus

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Atitaya Hitakarun ◽  
Sarawut Khongwichit ◽  
Nitwara Wikan ◽  
Sittiruk Roytrakul ◽  
Sutee Yoksan ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Dengue Virus ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Zika Virus ◽  
Chikungunya Virus ◽  
Encephalitis Virus ◽  
Virus Zika

scholarly journals NS5 from Dengue Virus Serotype 2 Can Adopt a Conformation Analogous to That of Its Zika Virus and Japanese Encephalitis Virus Homologues

2019 ◽  
Vol 94 (1) ◽  
Author(s):  
Abbas El Sahili ◽  
Tingjin Sherryl Soh ◽  
Jonas Schiltz ◽  
Aïcha Gharbi-Ayachi ◽  
Cheah Chen Seh ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Zika Virus ◽  
Nonstructural Protein ◽  
Vaccine Design ◽  
Encephalitis Virus ◽  
Virus Serotype ◽  
In Cells

ABSTRACT Flavivirus nonstructural protein 5 (NS5) contains an N-terminal methyltransferase (MTase) domain and a C-terminal polymerase (RNA-dependent RNA polymerase [RdRp]) domain fused through a 9-amino-acid linker. While the individual NS5 domains are structurally conserved, in the full-length protein, their relative orientations fall into two classes: the NS5 proteins from Japanese encephalitis virus (JEV) and Zika virus (ZIKV) adopt one conformation, while the NS5 protein from dengue virus serotype 3 (DENV3) adopts another. Here, we report a crystallographic structure of NS5 from DENV2 in a conformation similar to the extended one seen in JEV and ZIKV NS5 crystal structures. Replacement of the DENV2 NS5 linker with DENV1, DENV3, DENV4, JEV, and ZIKV NS5 linkers had modest or minimal effects on in vitro DENV2 MTase and RdRp activities. Heterotypic DENV NS5 linkers attenuated DENV2 replicon growth in cells, while the JEV and ZIKV NS5 linkers abolished replication. Thus, the JEV and ZIKV linkers likely hindered essential DENV2 NS5 interactions with other viral or host proteins within the virus replicative complex. Overall, this work sheds light on the dynamics of the multifunctional flavivirus NS5 protein and its interdomain linker. Targeting the NS5 linker is a possible strategy for producing attenuated flavivirus strains for vaccine design. IMPORTANCE Flaviviruses include important human pathogens, such as dengue virus and Zika virus. NS5 is a nonstructural protein essential for flavivirus RNA replication with dual MTase and RdRp enzyme activities and thus constitutes a major drug target. Insights into NS5 structure, dynamics, and evolution should inform the development of antiviral inhibitors and vaccine design. We found that NS5 from DENV2 can adopt a conformation resembling that of NS5 from JEV and ZIKV. Replacement of the DENV2 NS5 linker with the JEV and ZIKV NS5 linkers abolished DENV2 replication in cells, without significantly impacting in vitro DENV2 NS5 enzymatic activities. We propose that heterotypic flavivirus NS5 linkers impede DENV2 NS5 protein-protein interactions that are essential for virus replication.

scholarly journals Seroprevalence of Flavivirus Neutralizing Antibodies in Thailand by High-Throughput Neutralization Assay: Endemic Circulation of Zika Virus before 2012

mSphere ◽  
2021 ◽  
Author(s):  
Atsushi Yamanaka ◽  
Mami Matsuda ◽  
Tamaki Okabayashi ◽  
Pannamthip Pitaksajjakul ◽  
Pongrama Ramasoota ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
High Throughput ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Neutralization Assay ◽  
Encephalitis Virus ◽  
Antibody Detection ◽  
Luciferase Gene

Neutralization tests are the most reliable assay for flavivirus antibody detection; however, these assays are not suitable for high-throughput processing due to their time-consuming and labor-intensive nature. In this study, we developed single-round infectious particles (SRIPs) with a luciferase gene for dengue virus types 1 to 4, Japanese encephalitis virus, and Zika virus for use in a safe, high-throughput neutralization assay.

scholarly journals Human MxB Inhibits the Replication of Hepatitis C Virus

2018 ◽  
Vol 93 (1) ◽  
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.

Simultaneous detection of Dengue virus, Chikungunya virus, Zika virus, Yellow fever virus and West Nile virus

2019 ◽  
Vol 268 ◽  
pp. 53-55 ◽  
Author(s):  
José A. Boga ◽  
Marta E. Alvarez-Arguelles ◽  
Susana Rojo-Alba ◽  
Mercedes Rodríguez ◽  
María de Oña ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Dengue Virus ◽  
Yellow Fever ◽  
Zika Virus ◽  
Chikungunya Virus ◽  
Yellow Fever Virus ◽  
Simultaneous Detection ◽  
Fever Virus ◽  
West Nile ◽  
Virus Zika

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

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.

scholarly journals Japanese encephalitis virus–primed CD8+ T cells prevent antibody-dependent enhancement of Zika virus pathogenesis

2020 ◽  
Vol 217 (9) ◽  
Author(s):  
Dong Chen ◽  
Zhiliang Duan ◽  
Wenhua Zhou ◽  
Weiwei Zou ◽  
Shengwei Jin ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Replication ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Cd8 T Cells ◽  
Zika Virus ◽  
Encephalitis Virus ◽  
Protective Effects ◽  
Zikv Infection ◽  
Lethal Effects

Cross-reactive anti-flaviviral immunity can influence the outcome of infections with heterologous flaviviruses. However, it is unclear how the interplay between cross-reactive antibodies and T cells tilts the balance toward pathogenesis versus protection during secondary Zika virus (ZIKV) and Japanese encephalitis virus (JEV) infections. We show that sera and IgG from JEV-vaccinated humans and JEV-inoculated mice cross-reacted with ZIKV, exacerbated lethal ZIKV infection upon transfer to mice, and promoted viral replication and mortality upon ZIKV infection of the neonates born to immune mothers. In contrast, transfer of CD8+ T cells from JEV-exposed mice was protective, reducing the viral burden and mortality of ZIKV-infected mice and abrogating the lethal effects of antibody-mediated enhancement of ZIKV infection in mice. Conversely, cross-reactive anti-ZIKV antibodies or CD8+ T cells displayed the same pathogenic or protective effects upon JEV infection, with the exception that maternally acquired anti-ZIKV antibodies had no effect on JEV infection of the neonates. These results provide clues for developing safe anti-JEV/ZIKV vaccines.

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