Evaluation of the genotype I Japanese encephalitis virus as a stable viral vector for foreign gene expression

Li, Chenxi; Zhang, Linjie; Chen, Xuan; Jiang, Daoyuan; Hu, Ji; Guo, Jingnan; Ding, Jingjing; Jiao, Xiaoguo; Bao, Wenbin; Lǐ, Yànhuá

doi:10.1016/j.antiviral.2023.105652

Cited by 3 publications

(1 citation statement)

References 34 publications

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“…Both inactivated and live attenuated vaccines have been employed, the latter appearing to be most effective [ 70 ]. There is a large body of research on newer vaccine candidates, including recombinant protein [ 71 ], plasmid DNA [ 72 ], lentiviral vector [ 73 ], virus-like particle [ 74 ], mRNA lipid nanoparticle vaccine [ 75 ], and recombinant live vaccines based on the Genotype I backbone [ 67 , 76 ]. It is unlikely that any of the veterinary vaccines currently used in the endemic region would be acceptable for importation and use in the US in an emergency without considerable additional study, and the newer candidates are early in development.…”

Section: Vaccines As a Countermeasurementioning

confidence: 99%

Japanese Encephalitis: Risk of Emergence in the United States and the Resulting Impact

Monath

2023

Viruses

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Japanese encephalitis virus is a mosquito-borne member of the Flaviviridae family. JEV is the leading cause of viral encephalitis in Asia and is characterized by encephalitis, high lethality, and neurological sequelae in survivors. The virus also causes severe disease in swine, which are an amplifying host in the transmission cycle, and in horses. US agricultural authorities have recently recognized the threat to the swine industry and initiated preparedness activities. Other mosquito-borne viruses exotic to the Western Hemisphere have been introduced and established in recent years, including West Nile, Zika, and chikungunya viruses, and JEV has recently invaded continental Australia for the first time. These events amply illustrate the potential threat of JEV to US health security. Susceptible indigenous mosquito vectors, birds, feral and domestic pigs, and possibly bats, constitute the receptive ecological ingredients for the spread of JEV in the US. Fortunately, unlike the other virus invaders mentioned above, an inactivated whole virus JE vaccine (IXIARO®) has been approved by the US Food and Drug Administration for human use in advance of a public health emergency, but there is no veterinary vaccine. This paper describes the risks and potential consequences of the introduction of JEV into the US, the need to integrate planning for such an event in public health policy, and the requirement for additional countermeasures, including antiviral drugs and an improved single dose vaccine that elicits durable immunity in both humans and livestock.

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Section: Vaccines As a Countermeasurementioning

confidence: 99%

Japanese Encephalitis: Risk of Emergence in the United States and the Resulting Impact

Monath

2023

Viruses

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Isolation and identification of a duck-derived Japanese encephalitis virus and evaluation of its virulence in mice

Li,

Zhang,

Tang

et al. 2024

Veterinary Microbiology

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DDX3 regulates the cap-independent translation of the Japanese encephalitis virus via its interactions with PABP1 and the untranslated regions of the viral genome

Li,

Zhang,

Tang

et al. 2024

Preprint

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The translation of global cellular proteins is almost completely repressed in cells with flavivirus infection, while viral translation remains efficient. The mechanisms of flaviviruses evade host translational shutoff are largely unknown. Here, we identified viral elements and host factors associated with JEV evasion of host shutoff. JEV 5′UTR lacked IRES or IRES-like activity, while noncapped 5′UTR initiated translation in the presence of 3′UTR. Furthermore, the elements DB2 and sHP-SL within 3′UTR were involved in the regulation of cap-independent translation, which is conserved in the genusOrthoflavivirus. By RNA affinity purification and mass spectrometry analysis, cellular DDX3 and PABP1 were identified as key factors in regulating cap-independent translation of JEV via their interactions with DB2 and sHP-SL RNA structures. Mechanistically, we revealed that DDX3 could bind to both 5′UTR and 3′UTR of the JEV genome to establish a closed-loop architecture, recruit eIF4G/eIF4A to form the DDX3/PABP1/eIF4G/eIF4A tetrameric complex via its interaction with PABP1, thereby recruiting 43S PIC to the 5′-end of the JEV genome to start translation. Our findings demonstrated a noncanonical translation strategy employed by JEV and further revealed the regulatory roles of DDX3 and PABP1 in this mechanism. These results expand our knowledge of the translation initiation regulation in flaviviruses under the state of host translational shutoff, which provides a conserved antiviral target againstorthoflavivirus.

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Evaluation of the genotype I Japanese encephalitis virus as a stable viral vector for foreign gene expression

Cited by 3 publications

References 34 publications

Japanese Encephalitis: Risk of Emergence in the United States and the Resulting Impact

Japanese Encephalitis: Risk of Emergence in the United States and the Resulting Impact

Isolation and identification of a duck-derived Japanese encephalitis virus and evaluation of its virulence in mice

DDX3 regulates the cap-independent translation of the Japanese encephalitis virus via its interactions with PABP1 and the untranslated regions of the viral genome

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