Changing Geographic Distribution of Japanese Encephalitis Virus Genotypes, 1935–2017

Abstract

Japanese encephalitis virus (JEV) is a representative virus of the JEV serogroup in genus Flavivirus, family Flaviviridae. JEV is a mosquito-borne virus that causes Japanese encephalitis (JE), one of the most severe viral encephalitis diseases in the world. JEV is divided into five genotypes (G1-G5), and each genotype has its own distribution pattern. However, the distribution of different JEV genotypes has changed markedly in recent years. JEV G1 has replaced G3 as the dominant genotype in the traditional epidemic areas in Asia, while G3 has spread from Asia to Europe and Africa and caused domestic JE cases in Africa. G2 and G5, which were endemic in Malaysia, exhibited great geographical changes as well. G2 migrated southward and led to prevalence of JE in Australia, while G5 emerged in China and South Korea after decades of silence. Along with these changes, JE occurred in some non-traditional epidemic regions as an emerging infectious disease. The regional changes in JEV pose a great threat to human health, leading to huge disease burdens. Therefore, it is of great importance to strengthen the monitoring of JEV as well as virus genotypes, especially in non-traditional epidemic areas.

Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages

“…JE is the top type of viral encephalitis in the world, posing a threat to the health of more than two billion people in twenty-four countries. The estimated annual case number is 69,000, with a global incidence of 1.8/100,000, causing 10,000-15,000 mortalities [2]. The case fatality of JE is 20% and can be 30% in children.…”

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

“…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).…”

Mosquito Cell-Derived Japanese Encephalitis Virus-Like Particles Induce Specific Humoral and Cellular Immune Responses in Mice

“…The Japanese encephalitis virus (JEV) is a mosquito-borne arbovirus that belongs to the genus Flavivirus. An estimated 50,000-175,000 cases of JEV occur annually in Asia [1,2]. Potential outbreaks of JEV occur in Africa [3] and Europe [4][5][6].…”

“…Despite the fact that a JEV infection is responsible for an annual loss of 709,000 disability-adjusted life years [8], no antiviral interventions to control JEV infection have yet been approved [9]. JEV GIII immunization programs have proven effective in controlling JEV [10]; however, subsequent JEV genotype I (GI) displacement and poor protective efficacy against JEV genotype V (GV) suggest that an improved vaccine is needed [2,11,12]. New classes of JEV vaccines, such as protein subunit vaccines, DNA vaccines, viral vectors, and vaccines based on virus-like particles (VLPs) have yet to undergo extensive pre-clinical testing [13]; however, research on VLP-based vaccines is gaining traction [14,15].…”