scholarly journals Nucleolar Protein B23 Interacts with Japanese Encephalitis Virus Core Protein and Participates in Viral Replication

2006 ◽  
Vol 50 (3) ◽  
pp. 225-234 ◽  
Author(s):  
Yoshimi Tsuda ◽  
Yoshio Mori ◽  
Takayuki Abe ◽  
Tetsuo Yamashita ◽  
Toru Okamoto ◽  
...  
Keyword(s):  
Viral Replication ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Core Protein ◽  
Encephalitis Virus ◽  
Nucleolar Protein ◽  
Virus Core ◽  
Protein B23

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.

scholarly journals Nuclear Localization of Japanese Encephalitis Virus Core Protein Enhances Viral Replication

2005 ◽  
Vol 79 (6) ◽  
pp. 3448-3458 ◽  
Author(s):  
Yoshio Mori ◽  
Tamaki Okabayashi ◽  
Tetsuo Yamashita ◽  
Zijiang Zhao ◽  
Takaji Wakita ◽  
...  
Keyword(s):  
Japanese Encephalitis Virus ◽  
Cell Lines ◽  
Japanese Encephalitis ◽  
Nuclear Localization ◽  
Mammalian Cells ◽  
Core Protein ◽  
Encephalitis Virus ◽  
Wild Type ◽  
The Core

ABSTRACT Japanese encephalitis virus (JEV) core protein was detected in both the nucleoli and cytoplasm of mammalian and insect cell lines infected with JEV or transfected with the expression plasmid of the core protein. Mutation analysis revealed that Gly42 and Pro43 in the core protein are essential for the nuclear and nucleolar localization. A mutant M4243 virus in which both Gly42 and Pro43 were replaced by Ala was recovered by plasmid-based reverse genetics. In C6/36 mosquito cells, the M4243 virus exhibited RNA replication and protein synthesis comparable to wild-type JEV, whereas propagation in Vero cells was impaired. The mutant core protein was detected in the cytoplasm but not in the nucleus of either C6/36 or Vero cell lines infected with the M4243 virus. The impaired propagation of M4243 in mammalian cells was recovered by the expression of wild-type core protein in trans but not by that of the mutant core protein. Although M4243 mutant virus exhibited a high level of neurovirulence comparable to wild-type JEV in spite of the approximately 100-fold-lower viral propagation after intracerebral inoculation to 3-week-old mice of strain Jcl:ICR, no virus was recovered from the brain after intraperitoneal inoculation of the mutant. These results indicate that nuclear localization of JEV core protein plays crucial roles not only in the replication in mammalian cells in vitro but also in the pathogenesis of encephalitis induced by JEV in vivo.

scholarly journals 3′ cis-Acting Elements That Contribute to the Competence and Efficiency of Japanese Encephalitis Virus Genome Replication: Functional Importance of Sequence Duplications, Deletions, and Substitutions

2009 ◽  
Vol 83 (16) ◽  
pp. 7909-7930 ◽  
Author(s):  
Sang-Im Yun ◽  
Yu-Jeong Choi ◽  
Byung-Hak Song ◽  
Young-Min Lee
Keyword(s):  
Viral Replication ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Rna Replication ◽  
Encephalitis Virus ◽  
Protein Accumulation ◽  
Genomic Rna ◽  
Human Neuroblastoma ◽  
Lethal Mutant ◽  
Positive Strand Rna

ABSTRACT The positive-strand RNA genome of Japanese encephalitis virus (JEV) terminates in a highly conserved 3′-noncoding region (3′NCR) of six domains (V, X, I, II-1, II-2, and III in the 5′-to-3′ direction). By manipulating the JEV genomic RNA, we have identified important roles for RNA elements present within the 574-nucleotide 3′NCR in viral replication. The two 3′-proximal domains (II-2 and III) were sufficient for RNA replication and virus production, whereas the remaining four (V, X, I, and II-1) were dispensable for RNA replication competence but required for maximal replication efficiency. Surprisingly, a lethal mutant lacking all of the 3′NCR except domain III regained viability through pseudoreversion by duplicating an 83-nucleotide sequence from the 3′-terminal region of the viral open reading frame. Also, two viable mutants displayed severe genetic instability; these two mutants rapidly developed 12 point mutations in domain II-2 in the mutant lacking domains V, X, I, and II-1 and showed the duplication of seven upstream sequences of various sizes at the junction between domains II-1 and II-2 in the mutant lacking domains V, X, and I. In all cases, the introduction of these spontaneous mutations led to an increase in RNA production that paralleled the level of protein accumulation and virus yield. Interestingly, the mutant lacking domains V, X, I, and II-1 was able to replicate in hamster BHK-21 and human neuroblastoma SH-SY5Y cells but not in mosquito C6/36 cells, indicating a cell type-specific restriction of its viral replication. Thus, our findings provide the basis for a detailed map of the 3′ cis-acting elements in JEV genomic RNA, which play an essential role in viral replication. They also provide experimental evidence for the function of 3′ direct repeat sequences and suggest possible mechanisms for the emergence of these sequences in the 3′NCR of JEV and perhaps in other flaviviruses.

scholarly journals Pathogenesis and Host Immune Response during Japanese Encephalitis Virus Infection

2021 ◽  
Author(s):  
Swatantra Kumar ◽  
Rajni Nyodu ◽  
Vimal K. Maurya ◽  
Shailendra K. Saxena
Keyword(s):  
Cell Death ◽  
Viral Replication ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Immune Escape ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Encephalitis Virus ◽  
Japanese Encephalitis Virus Infection ◽  
Human Dermis

Japanese Encephalitis Virus (JEV) is a mosquito borne flavivirus infection. Transmission of JEV starts with the infected mosquito bite where human dermis layer act as the primary site of infection. Once JEV makes its entry into blood, it infects monocytes wherein the viral replication peaks up without any cell death and results in production of TNF-α.One of the most characteristics pathogenesis of JEV is the breaching of blood brain barrier (BBB). JEV propagation occurs in neurons that results in neuronal cell death as well as dissemination of virus into astrocytes and microglia leading to overexpression of proinflammatory cytokines. JEV infection results in host cells mediated secretion of various types of cytokines including type-1 IFN along with TNF-α and IFN-γ. Molecule like nitrous oxide (NO) exhibits antiviral activities against JEV infection and helps in inhibiting the viral replication by blocking protein synthesis and viral RNA and also in virus infected cells clearance. In addition, the antibody can also acts an opsonizing agent in order to facilitate the phagocytosis of viral particles, which is mediated by Fc or C3 receptor. This chapter focuses on the crucial mechanism of JEV induced pathogenesis including neuropathogenesis viral clearance mechanisms and immune escape strategies.

scholarly journals Origin and Evolution of Japanese Encephalitis Virus in Southeast Asia

2003 ◽  
Vol 77 (5) ◽  
pp. 3091-3098 ◽  
Author(s):  
Tom Solomon ◽  
Haolin Ni ◽  
David W. C. Beasley ◽  
Miquel Ekkelenkamp ◽  
Mary Jane Cardosa ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Southeast Asia ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Core Protein ◽  
Sequence Data ◽  
Encephalitis Virus ◽  
Epidemic Encephalitis ◽  
Amino Acid Divergence

ABSTRACT Since it emerged in Japan in the 1870s, Japanese encephalitis has spread across Asia and has become the most important cause of epidemic encephalitis worldwide. Four genotypes of Japanese encephalitis virus (JEV) are presently recognized (representatives of genotypes I to III have been fully sequenced), but its origin is not known. We have determined the complete nucleotide and amino acid sequence of a genotype IV Indonesian isolate (JKT6468) which represents the oldest lineage, compared it with other fully sequenced genomes, and examined the geographical distribution of all known isolates. JKT6468 was the least similar, with nucleotide divergence ranging from 17.4 to 19.6% and amino acid divergence ranging from 4.7 to 6.5%. It included an unusual series of amino acids at the carboxy terminus of the core protein unlike that seen in other JEV strains. Three signature amino acids in the envelope protein (including E327 Leu→Thr/Ser on the exposed lateral surface of the putative receptor binding domain) distinguished genotype IV strains from more recent genotypes. Analysis of all 290 JEV isolates for which sequence data are available showed that the Indonesia-Malaysia region has all genotypes of JEV circulating, whereas only more recent genotypes circulate in other areas (P < 0.0001). These results suggest that JEV originated from its ancestral virus in the Indonesia-Malaysia region and evolved there into the different genotypes which then spread across Asia. Our data, together with recent evidence on the origins of other emerging viruses, including dengue virus and Nipah virus, imply that tropical southeast Asia may be an important zone for emerging pathogens.

scholarly journals Screening of FDA-Approved Drugs for Inhibitors of Japanese Encephalitis Virus Infection

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Shaobo Wang ◽  
Yang Liu ◽  
Jiao Guo ◽  
Peilin Wang ◽  
Leike Zhang ◽  
...  
Keyword(s):  
Virus Infection ◽  
Viral Replication ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Transmembrane Domain ◽  
Specific Treatment ◽  
Encephalitis Virus ◽  
Japanese Encephalitis Virus Infection ◽  
Approved Drugs ◽  
Fda Approved Drugs

ABSTRACT Japanese encephalitis virus (JEV), an arthropod-borne flavivirus, is a major cause of acute viral encephalitis in humans. No approved drug is available for the specific treatment of JEV infections, and the available vaccines are not effective against all clinical JEV isolates. In the study described here, a high-throughput screening of an FDA-approved drug library for inhibitors of JEV was performed. Five hit drugs that inhibited JEV infection with a selective index of >10 were identified. The antiviral activities of these five hit drugs against other flavivirus, including Zika virus, were also validated. As three of the five hit drugs were calcium inhibitors, additional types of calcium inhibitors that confirmed that calcium is essential for JEV infection, most likely during viral replication, were utilized. Adaptive mutant analysis uncovered that replacement of Q130, located in transmembrane domain 3 of the nonstructural NS4B protein, which is relatively conserved in flaviviruses, with R or K conferred JEV resistance to manidipine, a voltage-gated Ca2+ channel (VGCC) inhibitor, without an apparent loss of the viral growth profile. Furthermore, manidipine was indicated to protect mice against JEV-induced lethality by decreasing the viral load in the brain, while it abrogated the histopathological changes associated with JEV infection. This study provides five antiflavivirus candidates and identifies cytoplasmic calcium to be a novel antiviral target for the treatment of JEV infection. The findings reported here provide therapeutic possibilities for combating infections caused by flaviviruses. IMPORTANCE No approved therapy for the treatment of Japanese encephalitis virus infection is currently available. Repurposing of approved drugs would accelerate the development of a therapeutic stratagem. In this study, we screened a library of FDA-approved drugs and identified five hit drugs, especially calcium inhibitors, exerting antiflavivirus activity that blocked viral replication. The in vivo efficacy and toxicity of manidipine were investigated with a mouse model of JEV infection, and the viral target was identified by generating an adaptive mutant.

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