scholarly journals Amino Acid at Position 166 of NS2A in Japanese Encephalitis Virus (JEV) Is Associated with In Vitro Growth Characteristics of JEV

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 709
Author(s):  
Shigeru Tajima ◽  
Satoshi Taniguchi ◽  
Eri Nakayama ◽  
Takahiro Maeki ◽  
Takuya Inagaki ◽  
...  
Keyword(s):  
Amino Acid ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Neuroblastoma Cells ◽  
Encephalitis Virus ◽  
Growth Potential ◽  
Sequencing Analysis ◽  
Murine Neuroblastoma ◽  
Growth Ability

We previously showed that the growth ability of the Japanese encephalitis virus (JEV) genotype V (GV) strain Muar is clearly lower than that of the genotype I (GI) JEV strain Mie/41/2002 in murine neuroblastoma cells. Here, we sought to identify the region in GV JEV that is involved in its low growth potential in cultured cells. An intertypic virus containing the NS1-3 region of Muar in the Mie/41/2002 backbone (NS1-3Muar) exhibited a markedly diminished growth ability in murine neuroblastoma cells. Moreover, the growth rate of a Muar NS2A-bearing intertypic virus (NS2AMuar) was also similar to that of Muar in these cells, indicating that NS2A of Muar is one of the regions responsible for the Muar-specific growth ability in murine neuroblastoma cells. Sequencing analysis of murine neuroblastoma Neuro-2a cell-adapted NS1-3Muar virus clones revealed that His-to-Tyr mutation at position 166 of NS2A (NS2A166) could rescue the low replication ability of NS1-3Muar in Neuro-2a cells. Notably, a virus harboring a Tyr-to-His substitution at NS2A166 (NS2AY166H) showed a decreased growth ability relative to that of the parental virus Mie/41/2002, whereas an NS2AMuar-based mutant virus, NS2AMuar-H166Y, showed a higher growth ability than NS2AMuar in Neuro-2a cells. Thus, these results indicate that the NS2A166 amino acid in JEV is critical for the growth and tissue tropism of JEV in vitro.

scholarly journals A Single Amino Acid Substitution in the NS2A Protein of Japanese Encephalitis Virus Affects Virus PropagationIn Vitrobut NotIn Vivo

2015 ◽  
Vol 89 (11) ◽  
pp. 6126-6130 ◽  
Author(s):  
Yuki Takamatsu ◽  
Kouichi Morita ◽  
Daisuke Hayasaka
Keyword(s):  
Amino Acid ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Encephalitis Virus ◽  
Single Amino Acid ◽  
Virus Propagation ◽  
Viral Loads ◽  
Unique Amino Acid

We identified a unique amino acid of NS2A113, phenylalanine, that affects the efficient propagation of two Japanese encephalitis virus strains, JaTH160 and JaOArS982, in neuroblastoma Neuro-2a cells but not in cell lines of extraneural origin. This amino acid did not affect viral loads in the brain or survival curves in mice. These findings suggest that virus propagationin vitromay not reflect the level of virus neuroinvasivenessin vivo.

scholarly journals An amino acid substitution (V3I) in the Japanese encephalitis virus NS4A protein increases its virulence in mice, but not its growth rate in vitro

2011 ◽  
Vol 92 (7) ◽  
pp. 1601-1606 ◽  
Author(s):  
Yukie Yamaguchi ◽  
Yoko Nukui ◽  
Shigeru Tajima ◽  
Reiko Nerome ◽  
Fumihiro Kato ◽  
...  
Keyword(s):  
Amino Acid ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Amino Acid Substitution ◽  
Encephalitis Virus ◽  
Virus Growth ◽  
High Virulence ◽  
Isoleucine Residue

Our previous studies have shown that the Japanese encephalitis virus (JEV) strain Mie/40/2004 is the most virulent of the strains isolated by us in Japan from 2002 to 2004. Comparison of the amino acid sequence of Mie/40/2004 with those of low-virulence strains revealed that an isoleucine residue at position 3 of the Mie/40/2004 NS4A protein may increase viral pathogenicity. A recombinant virus with a single valine-to-isoleucine substitution (V3I) at position 3 in the low-virulence Mie/41/2002 background (rJEV-Mie41-NS4AV3I) exhibited increased virulence in mice compared with the Mie/41/2002 parent strain. The V3I mutation did not affect virus growth in several cell lines. These results demonstrate that the isoleucine at position 3 in the NS4A protein of Mie/40/2004 is responsible for its high virulence in vivo. This is the first report to show that an amino acid substitution in a flavivirus NS4A protein alters viral pathogenicity in mice.

scholarly journals Potential Role of Birds in Japanese Encephalitis Virus Zoonotic Transmission and Genotype Shift

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 357
Author(s):  
Muddassar Hameed ◽  
Abdul Wahaab ◽  
Mohsin Nawaz ◽  
Sawar Khan ◽  
Jawad Nazir ◽  
...  
Keyword(s):  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Encephalitis Virus ◽  
Zoonotic Transmission ◽  
In Vivo Studies ◽  
Genotype I ◽  
Genotype Iii

Japanese encephalitis (JE) is a vaccine-preventable disease caused by the Japanese encephalitis virus (JEV), which is primarily prevalent in Asia. JEV is a Flavivirus, classified into a single serotype with five genetically distinct genotypes (I, II, III, IV, and V). JEV genotype III (GIII) had been the most dominant strain and caused numerous outbreaks in the JEV endemic countries until 1990. However, recent data shows the emergence of JEV genotype I (GI) as a dominant genotype and it is gradually displacing GIII. The exact mechanism of this genotype displacement is still unclear. The virus can replicate in mosquito vectors and vertebrate hosts to maintain its zoonotic life cycle; pigs and aquatic wading birds act as an amplifying/reservoir hosts, and the humans and equines are dead-end hosts. The important role of pigs as an amplifying host for the JEV is well known. However, the influence of other domestic animals, especially birds, that live in high abundance and close proximity to the human is not well studied. Here, we strive to briefly highlight the role of birds in the JEV zoonotic transmission, discovery of birds as a natural reservoirs and amplifying host for JEV, species of birds susceptible to the JEV infection, and the proposed effect of JEV on the poultry industry in the future, a perspective that has been neglected for a long time. We also discuss the recent in vitro and in vivo studies that show that the newly emerged GI viruses replicated more efficiently in bird-derived cells and ducklings/chicks than GIII, and an important role of birds in the JEV genotype shift from GIII to GI.

scholarly journals Targeting of the Nasal Mucosa by Japanese Encephalitis Virus for Non-Vector-Borne Transmission

2018 ◽  
Vol 92 (24) ◽  
Author(s):  
Obdulio García-Nicolás ◽  
Roman O. Braun ◽  
Panagiota Milona ◽  
Marta Lewandowska ◽  
Ronald Dijkman ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Ex Vivo ◽  
Encephalitis Virus ◽  
Nasal Epithelium ◽  
Virus Shedding ◽  
Nasal Epithelial Cells ◽  
Vector Borne

ABSTRACTThe mosquito-borne Japanese encephalitis virus (JEV) causes severe central nervous system diseases and cycles betweenCulexmosquitoes and different vertebrates. For JEV and some other flaviviruses, oronasal transmission is described, but the mode of infection is unknown. Using nasal mucosal tissue explants and primary porcine nasal epithelial cells (NEC) at the air-liquid interface (ALI) and macrophages asex vivoandin vitromodels, we determined that the nasal epithelium could represent the route of entry and exit for JEV in pigs. Porcine NEC at the ALI exposed to with JEV resulted in apical and basolateral virus shedding and release of monocyte recruiting chemokines, indicating infection and replication in macrophages. Moreover, macrophages stimulated by alarmins, including interleukin-25, interleukin-33, and thymic stromal lymphopoietin, were more permissive to the JEV infection. Altogether, our data are important to understand the mechanism of non-vector-borne direct transmission of Japanese encephalitis virus in pigs.IMPORTANCEJEV, a main cause of severe viral encephalitis in humans, has a complex ecology composed of a mosquito-waterbird cycle and a cycle involving pigs, which amplifies virus transmission to mosquitoes, leading to increased human cases. JEV can be transmitted between pigs by contact in the absence of arthropod vectors. Moreover, virus or viral RNA is found in oronasal secretions and the nasal epithelium. Using nasal mucosa tissue explants and three-dimensional porcine nasal epithelial cells cultures and macrophages asex vivoandin vitromodels, we determined that the nasal epithelium could be a route of entry as well as exit for the virus. Infection of nasal epithelial cells resulted in apical and basolateral virus shedding and release of monocyte recruiting chemokines and therefore infection and replication in macrophages, which is favored by epithelial-cell-derived cytokines. The results are relevant to understand the mechanism of non-vector-borne direct transmission of JEV.

scholarly journals Phenotypic and Genotypic Comparison of a Live-Attenuated Genotype I Japanese Encephalitis Virus SD12-F120 Strain with Its Virulent Parental SD12 Strain

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 552 ◽  
Author(s):  
Muhammad Naveed Anwar ◽  
Xin Wang ◽  
Muddassar Hameed ◽  
Abdul Wahaab ◽  
Chenxi Li ◽  
...  
Keyword(s):  
Amino Acid ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Clinical Symptoms ◽  
Encephalitis Virus ◽  
Amino Acid Substitutions ◽  
Genotype I ◽  
Genetic Changes ◽  
Genotypic Characteristics ◽  
Insight Into

The phenotypic and genotypic characteristics of a live-attenuated genotype I (GI) strain (SD12-F120) of Japanese encephalitis virus (JEV) were compared with its virulent parental SD12 strain to gain an insight into the genetic changes acquired during the attenuation process. SD12-F120 formed smaller plaque on BHK-21 cells and showed reduced replication in mouse brains compared with SD12. Mice inoculated with SD12-F120 via either intraperitoneal or intracerebral route showed no clinical symptoms, indicating a highly attenuated phenotype in terms of both neuroinvasiveness and neurovirulence. SD12-F120 harbored 29 nucleotide variations compared with SD12, of which 20 were considered silent nucleotide mutations, while nine resulted in eight amino acid substitutions. Comparison of the amino acid variations of SD12-F120 vs. SD12 pair with those from other four isogenic pairs of the attenuated and their virulent parental strains revealed that the variations at E138 and E176 positions of E protein were identified in four and three pairs, respectively, while the remaining amino acid variations were almost unique to their respective strain pairs. These observations suggest that the genetic changes acquired during the attenuation process were likely to be strain-specific and that the mechanisms associated with JEV attenuation/virulence are complicated.

scholarly journals Comparison of genomic and amino acid sequences of eight Japanese encephalitis virus isolates from bats

2013 ◽  
Vol 158 (12) ◽  
pp. 2543-2552 ◽  
Author(s):  
Shan Liu ◽  
Xing Li ◽  
Zhiyong Chen ◽  
Yixiong Chen ◽  
Qionghua Zhang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Amino Acid Sequences ◽  
Encephalitis Virus ◽  
Virus Isolates
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