A model to study neurotropism and persistency of Japanese encephalitis virus infection in human neuroblastoma cells and leukocytes.
Japanese encephalitis (JE) is the most common mosquito-borne encephalitis in the Asia-Pacific region. Patients with JE usually present neuronal involvement, but other organ involvement is relatively rare. Employing human neuroblast-derived (NB) cell lines and different blood cells (erythrocytes, lymphocytes, granulocytes and monocytes), the neurotropism and persistency of Japanese encephalitis virus (JEV) in human cells was investigated. It was found that JEV could not replicate in erythrocytes, granulocytes or lymphocytes. Monocytes and NB cell lines could support replication of JEV as demonstrated by expression of viral NS3 antigen and virus plaque-forming units (p.f.u.). JEV could replicate more efficiently in neuroblastoma (HTB-11) cells than in monocytes after infection for 48 h (2.1+/-1.2x10(7) vs 2.8+/-0.7x10(2) p.f.u. ml(-1)). Two different strains of JEV revealed a similar infectivity to different leukocytes and four NB cell lines. In a kinetic study, it was found that JEV-infected monocytes possessed a high viability (90 %) after infection for 5 days, while JEV-infected neuroblastoma cells suffered cell apoptosis in 2 days and decreased viability to less than 1 % in 5 days. Further studies showed that monocytes could take up JEV rapidly, displaying a log scale increase of intracellular JEV titres in 9 h after infection. Significantly, extracellular production of JEV by monocytes started in 12 h, peaked in 3 days and persisted for more than 3 weeks. These results suggest that JEV-infected monocytes may play an important role in harbouring JEV for eventual transmission to NB cells and that modulation of JEV-induced NB cell apoptosis may be useful in treating patients with JE.
Yang
Kuender D
KD
Chang Gung Children's Hospital at Kaohsiung, Chang Gung University, 123 Ta-Pei Road, Niau-Sung, Kaohsiung 833, Taiwan.
Yeh
Wen-Ting
WT
Chang Gung Children's Hospital at Kaohsiung, Chang Gung University, 123 Ta-Pei Road, Niau-Sung, Kaohsiung 833, Taiwan.
Chen
Rong-Fu
RF
Chang Gung Children's Hospital at Kaohsiung, Chang Gung University, 123 Ta-Pei Road, Niau-Sung, Kaohsiung 833, Taiwan.
Chuon
Hui-Lan
HL
Department of Pathology, National Defense Medical Center, Hung Kuang Institute of Technology, Sha-Lu, Taichung 433, Taiwan.
Tsai
Hui-Ping
HP
Department of Pathology, National Defense Medical Center, Hung Kuang Institute of Technology, Sha-Lu, Taichung 433, Taiwan.
Yao
Chen-Wen
CW
Department of Pathology, National Defense Medical Center, Hung Kuang Institute of Technology, Sha-Lu, Taichung 433, Taiwan.
Shaio
Men-Fang
MF
Department of Medical Research, Kuang Tien General Hospital, Hung Kuang Institute of Technology, Sha-Lu, Taichung 433, Taiwan.
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D045744:Cell Line, Tumor; D002470:Cell Survival; D009033:Culicidae; D004664:Encephalitis Virus, Japanese / Q000472:pathogenicity / Q000502:physiology*; D004672:Encephalitis, Japanese / Q000473:pathology / Q000821:virology; D004912:Erythrocytes / Q000821:virology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007303:Insect Vectors; D007962:Leukocytes / Q000821:virology*; D009447:Neuroblastoma / Q000473:pathology / Q000821:virology*; D009474:Neurons / Q000473:pathology / Q000821:virology*; D014779:Virus Replication
D000956:Antigens, Viral