TY - JOUR
T1 - A preliminary neuropathological study of Japanese encephalitis in humans and a mouse model
AU - German, Allison C.
AU - Myint, Khin Saw Aye
AU - Mai, Nguyen Thi Hoang
AU - Pomeroy, Ian
AU - Phu, Nguyen Hoan
AU - Tzartos, John
AU - Winter, Peter
AU - Collett, Jennifer
AU - Farrar, Jeremy
AU - Barrett, Alan
AU - Kipar, Anja
AU - Esiri, Margaret M.
AU - Solomon, Tom
N1 - Funding Information:
We thank the Director and staff of the Centre for Tropical Disease, Ho Chi Minh City for their support; the families of the Vietnamese patients agreeing to participate in this study; the Pathology Department for help with the autopsies; Gareth Turner for help setting up the study; the technical staff in the Department of Veterinary Pathology, Liverpool for assistance with immunohistological staining; David Ferguson at the Department of Neuropathology, Oxford, for help with electron microscopy; Ananda Nisalak, David Vaughn and colleagues at AFRIMS, Bangkok for assistance with diagnostic studies; and Dr V Ravi, Dr Anita Desai and Dr S. Shankar, National Institute of Mental Health and Neuro Sciences, Banglaore, India, for helpful discussions. This work was funded by the Wellcome Trust of Great Britain (Grant no. 054682). Tom Solomon is a UK Medical Research Council Senior Clinical Fellow.
PY - 2006/12
Y1 - 2006/12
N2 - Japanese encephalitis virus is a mosquito-borne flavivirus that causes approximately 10 000 deaths annually in Asia. After a brief viraemia, the virus enters the central nervous system, but the means of crossing the blood-brain barrier is uncertain. We used routine histological staining, immunohistology and electron microscopy to examine brain material from four fatal human cases, and made comparisons with material from a mouse model. In human material there was oedema, perivascular inflammation, haemorrhage, microglial nodules and acellular necrotic foci, as has been described previously. In addition, there was new evidence suggestive of viral replication in the vascular endothelium, with endothelial cell damage; this included occasional viral antigen staining, uneven binding of the vascular endothelial cells to Ulex europaeus agglutinin I and ultrastructural changes. Viral antigen was also found in neurons. There was an active astrocytic response, as shown by glial fibrillary acidic protein staining, and activation of microglial cells was demonstrated by an increase in major histocompatibility complex class II expression. Similar inflammatory infiltrates and a microglial reaction were observed in mouse brain tissue. In addition, β-amyloid precursor protein staining indicated impaired axonal transport. Whether these findings are caused by viral replication in the vascular endothelium or the immune response merits further investigation.
AB - Japanese encephalitis virus is a mosquito-borne flavivirus that causes approximately 10 000 deaths annually in Asia. After a brief viraemia, the virus enters the central nervous system, but the means of crossing the blood-brain barrier is uncertain. We used routine histological staining, immunohistology and electron microscopy to examine brain material from four fatal human cases, and made comparisons with material from a mouse model. In human material there was oedema, perivascular inflammation, haemorrhage, microglial nodules and acellular necrotic foci, as has been described previously. In addition, there was new evidence suggestive of viral replication in the vascular endothelium, with endothelial cell damage; this included occasional viral antigen staining, uneven binding of the vascular endothelial cells to Ulex europaeus agglutinin I and ultrastructural changes. Viral antigen was also found in neurons. There was an active astrocytic response, as shown by glial fibrillary acidic protein staining, and activation of microglial cells was demonstrated by an increase in major histocompatibility complex class II expression. Similar inflammatory infiltrates and a microglial reaction were observed in mouse brain tissue. In addition, β-amyloid precursor protein staining indicated impaired axonal transport. Whether these findings are caused by viral replication in the vascular endothelium or the immune response merits further investigation.
KW - Arbovirus
KW - Blood brain barrier
KW - Japanese encephalitis
KW - Zoonosis
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U2 - 10.1016/j.trstmh.2006.02.008
DO - 10.1016/j.trstmh.2006.02.008
M3 - Article
C2 - 16814333
AN - SCOPUS:33749071805
SN - 0035-9203
VL - 100
SP - 1135
EP - 1145
JO - Transactions of the Royal Society of Tropical Medicine and Hygiene
JF - Transactions of the Royal Society of Tropical Medicine and Hygiene
IS - 12
ER -