Japanese Encephalitis Virus Interaction with Mosquitoes: A Review of Vector Competence, Vector Capacity and Mosquito Immunity

Abstract

Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus and a major cause of human viral encephalitis in Asia. We provide an overview of the knowledge on vector competence, vector capacity, and immunity of mosquitoes in relation to JEV. JEV has so far been detected in more than 30 mosquito species. This does not necessarily mean that these species contribute to JEV transmission under field conditions. Therefore, vector capacity, which considers vector competence, as well as environmental, behavioral, cellular, and biochemical variables, needs to be taken into account. Currently, 17 species can be considered as confirmed vectors for JEV and 10 other species as potential vectors. Culex tritaeniorhynchus and Culex annulirostris are considered primary JEV vectors in endemic regions. Culex pipiens and Aedes japonicus could be considered as potentially important vectors in the case of JEV introduction in new regions. Vector competence is determined by various factors, including vector immunity. The available knowledge on physical and physiological barriers, molecular pathways, antimicrobial peptides, and microbiome is discussed in detail. This review highlights that much remains to be studied about vector immunity against JEV in order to identify novel strategies to reduce JEV transmission by mosquitoes.

Relevant Day/Night Temperatures Simulating Belgian Summer Conditions Reduce Japanese Encephalitis Virus Dissemination and Transmission in Belgian Field-Collected Culex pipiens Mosquitoes

“…In addition, no specific treatment is available [ 6 ]. JEV is currently endemic in Australia (Torres Strait islands) and Southeast and East Asia, including the temperate zone of north-eastern China, Japan and Korea [ 7 , 8 ], making up nearly half of the human population lives in countries at risk [ 9 ]. In 2022, it spread to new regions in Australia [ 10 ].…”

“…Current knowledge about vector competence and vector capacity of mosquitoes for JEV, as well as the limited knowledge about the underlying mechanisms affecting these parameters, was recently reviewed by our group [ 8 ]. Seventeen species have been reported to be able to transmit JEV in the laboratory and have additionally already been found positive in the field, namely Aedes albopictus, Aedes vexans, Aedes vigilax, Anopheles tessellatus, Armigeres subalbatus, Culex annulirostris, Culex bitaeniorhynchus, Culex fuscocephala, Cullex gelidus, Culex pipiens, Culex pipiens pallens, Culex pseudovishnui, Culex quinquefasciatus, Culex sitiens, Culex tarsalis, Culex tritaeniorhynchus and Culex vishnui , making them the currently known vectors for JEV.…”

Japanese Encephalitis Virus: An Emerging Threat in the Indo-Pacific Region

“…Recently, the C protein crystal structure was revealed and it was shown to have αhelixes 1-4 secondary structure, which closely resembles with the capsid protein of DENV, WNV, and ZIKV [21]. Each monomer of the JEV capsid protein consists of four helices: α1 (amino acid [29][30][31][32][33][34][35][36][37][38], α2 (amino acid 44-57), α3 (amino acid [63][64][65][66][67][68][69][70], and the longest α4 (amino acid , connected by short loops. The amino-terminal of α helix-1 forms closed and open confirmation by which it tends to be flexible and allows possible antivirals against this domain.…”

“…Thereafter, the virus gets replicated and virions burst out into the hemocoel from where it travels to the tracheal system and finally reaches the salivary glands [33]. Eventually, acinar cells of salivary glands become infected with the virus after passing the salivary gland infection barrier and start to shed virions into the saliva and the carrier mosquito ready to infect the subsequent host when it bites.Upon infected mosquito bites, virions finally released to the dermal cells of the healthy human [32], from where the virus causes either latent infection by infecting only mononuclear cells or persistent infection in which it invades the nervous system [34]. Pathogen-associated molecular patterns (PAMP) bind to pathogen recognition receptors (PRR) to induce interferon stimulatory genes (ISGs like PKR, OAS, TRIM21, ISG15, and MX1) via the JNK pathway.…”

Re-burying Artificially Exposed Surface of Viral Subunit Vaccines Through Oligomerization Enhances Vaccine Efficacy

“…Japanese encephalitis virus (JEV) is the leading cause of epidemic viral encephalitis in humans in Asian countries, with case fatality rates of ~25-30% ( Morita et al., 2015 ; Dong and Soong, 2021 ; Ramli et al., 2022 ; Xu et al., 2022 ). It is a member of the Flavivirus family and belongs to the arbovirus genus; this genus also includes human pathogens Zika virus (ZIKV), West Nile virus (WNV), Dengue virus (DENV), and Yellow Fever virus (YFV) ( Kuno et al., 1998 ; Van den Eynde et al., 2022 ). JEV is an enveloped and positive-stranded RNA virus.…”