Experimental Evaluation of the Role of Ecologically-Relevant Hosts and Vectors in Japanese Encephalitis Virus Genotype Displacement

Abstract

Japanese encephalitis virus (JEV) is a flavivirus that is maintained via transmission between Culex spp. mosquitoes and water birds across a large swath of southern Asia and northern Australia. Currently JEV is the leading cause of vaccine-preventable encephalitis in humans in Asia. Five genotypes of JEV (G-I–G-V) have been responsible for historical and current outbreaks in endemic regions, and G-I and G-III co-circulate throughout Southern Asia. While G-III has historically been the dominant genotype worldwide, G-I has gradually but steadily displaced G-III. The objective of this study was to better understand the phenomenon of genotype displacement for JEV by evaluating both avian host and mosquito vector susceptibilities to infection with representatives from both G-I and G-III. Since ducks and Culex quinquefasciatus mosquitoes are prevalent avian hosts and vectors perpetuating JEV transmission in JE endemic areas, experimental evaluation of virus replication in these species was considered to approximate the natural conditions necessary for studying the role of host, vectors and viral fitness in the JEV genotype displacement context. We evaluated viremia in ducklings infected with G-I and G-III, and did not detect differences in magnitude or duration of viremia. Testing the same viruses in mosquitoes revealed that the rates of infection, dissemination and transmission were higher in virus strains belonging to G-I than G-III, and that the extrinsic incubation period was shorter for the G-I strains. These data suggest that the characteristics of JEV infection of mosquitoes but not of ducklings, may have play a role in genotype displacement.

Serological Evidence for Japanese Encephalitis and West Nile Virus Infections in Domestic Birds in Cambodia

“…In addition, several experimental studies showed that domestic birds can be infected with JEV (5,14,15) and might even act as JEV reservoirs (39,40). However, it is controversially discussed if they develop a sufficient viremia to infect mosquitoes (14,(41)(42)(43). In our study, ducks were more likely to be seropositive when they are 10 months or older than chickens (87.1% of ducks seropositive compared to 33.3% of chickens of that age).…”

Perspectives Regarding the Risk of Introduction of the Japanese Encephalitis Virus (JEV) in the United States

“…Depending on the study, GI was shown to replicate more efficiently in pig, avian, and mosquito cells than GIII (10,47,48). Genotype I had a higher infection rate and shorter extrinsic incubation period than GIII during in vivo studies using C. quinquefasciatus (12). Whereas, these studies help to explain how GI might have displaced the previous genotype, other host and environmental factors, such as effects of immunity of a population to the different genotypes, changes in farming, and animal husbandry practices, and changes in migratory patterns of birds, may have also contributed to the emergence of GI.…”

“…Future genotype displacement or genetic modifications can compromise current cross-protection, and in turn threaten vaccine effectiveness, current immunization and other public health programs (12). Other challenges associated with emergence or reemergence of JEV genotypes could include changes in transmission paths, disease burden, or host demographics (11,84).…”

“…Having expanded from Japan, where it was first isolated, JEV has spread to all neighboring countries, now covering most regions in Southeast Asia. Besides the wide distribution of JEV, recent evidence of geographical genotype displacement has pointed to the changing dynamics of JEV transmission, raising public health concern regarding virus spread to susceptible regions of the globe (4,(10)(11)(12). Japanese encephalitis virus genetic material has already been identified in mosquitoes and birds collected in northern Italy, where human cases are unreported to date (13,14); concurrently, other arboviruses have been emerging in previously unaffected areas, with one of the most recent examples being the occurrence of outbreaks of Zika (although humans are reservoir of this virus) virus in South America (15).…”

Essential Oils of Zingiber Species from Vietnam: Chemical Compositions and Biological Activities

“…Vietnam is located in the tropics of Southeast Asia, and several mosquito-borne diseases are endemic, including Japanese encephalitis [ 1 ], dengue fever [ 2 ], and Zika [ 3 ]. Culex species are considered to be important vectors of Japanese encephalitis virus (JEV), including Culex quinquefasciatus Say (Diptera: Culicidae) [ 4 ], but other mosquito genera may also serve as competent vectors of the virus [ 5 , 6 ]. Dengue fever is hyperendemic to Vietnam with all four serotypes of the virus in circulation, resulting in periodic acute epidemics of both dengue fever and dengue hemorrhagic fever [ 7 , 8 ].…”