Growth, Pathogenesis, and Serological Characteristics of the Japanese Encephalitis Virus Genotype IV Recent Strain 19CxBa-83-Cv

Abstract

Genotype IV Japanese encephalitis (JE) virus (GIV JEV) is the least common and most neglected genotype in JEV. We evaluated the growth and pathogenic potential of the GIV strain 19CxBa-83-Cv, which was isolated from a mosquito pool in Bali, Indonesia, in 2019, and serological analyses were also conducted. The growth ability of 19CxBa-83-Cv in Vero cells was intermediate between that of the genotype I (GI) strain Mie/41/2002 and the genotype V (GV) strain Muar, whereas 19CxBa-83-Cv and Mie/41/2002 grew faster than Muar in mouse neuroblastoma cells. The neuroinvasiveness of 19CxBa-83-Cv in mice was higher than that of Mie/41/2002 but lower than that of Muar; however, there were no significant differences in neurovirulence in mice among the three strains. The neutralizing titers of sera from 19CxBa-83-Cv- and Mie/41/2002-inoculated mice against 19CxBa-83-Cv and Mie/41/2002 were similar, whereas the titers against Muar were lower than those of the other two viruses. The neutralizing titers of JE vaccine-inoculated mouse pool serum against 19CxBa-83-Cv and Muar were significantly lower than those against Mie/41/2002. The neutralizing titers against the three viruses were similar in three out of the five serum samples from GI-infected JE patients, although the titers against Mie/41/2002 were higher than those against 19CxBa-38-Cv and Muar in the remaining two sera samples. In summary, we identified the basic characteristics of 19CxBa-83-Cv, but further studies are needed to better understand GIV JEV.

Characterization of genotype V Japanese encephalitis virus isolates from Republic of Korea

“…To investigate virulence, mice were infected with the same titre of virus and observed the progression of disease over 15 days ( Figure 4 (B, C)). Previous studies have indicated that GV JEVs exhibit higher virulence than GIII in mice [ 21 , 26 ]. In our experiments, Mice infected with Muar showed a significant weight loss and higher mortality compared to the GIII Nakayama.…”

“…Particularly in vitro , differences were observed based on the type of cell line or the virus strain used for comparison. For example, GV strains typically showed similar propagation kinetics to GI and GIII JEVs in most cell lines but exhibited inefficient growth in neuroblastoma cells [ 14 , 26 ]. However, our results indicated that Muar exhibited lower in vitro propagation compared to Nakayama, even in BHK-21 fibroblast cells.…”

Neurovirulence of the Australian outbreak Japanese Encephalitis virus genotype 4 is lower compared to genotypes 2 and 3 in mice and human cortical brain organoids

“…Efforts to develop treatments for JEV neuropathology are hindered by the difficulties in diagnosing early infection 8 before the virus has infected central nervous system (CNS) neurons; and once the virus has infected CNS neurons, treatments must also be able to effectively enter the brain. In addition, mouse models of JEV neuropathology are often physiologically inappropriate, using intracranial routes of infection or very young mice [9][10][11] . Well-characterized, adult mouse models with high penetrance of JEV neuropathology after peripheral inoculation would represent useful tools to study mechanisms of infection and disease and evaluate potential new interventions.…”

“…Efforts to develop treatments for JEV neuropathology are hindered by the difficulties in diagnosing early infection (13) before the virus has infected central nervous system (CNS) neurons; and once the virus has infected CNS neurons, treatments must also be able to effectively enter the brain. While a range of JEV mouse models have been reported (Supplementary Table 1) (18), there are no studies of genotype 4 in adult mice, with the only study on genotype 4 JEV using 3-week-old mice (19). Well-characterized, adult mouse models of recent genotype 4 isolates would represent useful tools to study mechanisms of infection and disease and evaluate potential new interventions.…”

Characterisation of a Japanese Encephalitis virus genotype 4 isolate from the 2022 Australian outbreak

“…Efforts to develop treatments for JEV neuropathology are hindered by the difficulties in diagnosing early infection 13 before the virus has infected central nervous system (CNS) neurons; and once the virus has infected CNS neurons, treatments must also be able to effectively enter the brain. While a range of JEV mouse models have been reported (Supplementary Table 1) 19 , there are no studies of genotype 4 peripheral inoculation in adult mice, with the only studies on genotype 4 JEV using 3-week-old mice 20 or intracranial inoculation 21 . Well-characterized, adult mouse models of recent genotype 4 isolates would represent useful tools to study mechanisms of infection and disease and evaluate potential new interventions.…”