A systematic molecular pathology study of a laboratory confirmed H5N1 human case.
Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Uncertainty still exists, partly because of the limited number of cases analysed. In this study, a full autopsy including 5 organ systems was conducted on a confirmed H5N1 human fatal case (male, 42 years old) within 18 hours of death. In addition to the respiratory system (lungs, bronchus and trachea), virus was isolated from cerebral cortex, cerebral medullary substance, cerebellum, brain stem, hippocampus ileum, colon, rectum, ureter, aortopulmonary vessel and lymph-node. Real time RT-PCR evidence showed that matrix and hemagglutinin genes were positive in liver and spleen in addition to positive tissues with virus isolation. Immunohistochemistry and in-situ hybridization stains showed accordant evidence of viral infection with real time RT-PCR except bronchus. Quantitative RT-PCR suggested that a high viral load was associated with increased host responses, though the viral load was significantly different in various organs. Cells of the immunologic system could also be a target for virus infection. Overall, the pathogenesis of HPAI H5N1 virus was associated both with virus replication and with immunopathologic lesions. In addition, immune cells cannot be excluded from playing a role in dissemination of the virus in vivo.
Department of Influenza, Chinese National Influenza Center, State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Rongbao
R
Gao
Libo
L
Dong
Jie
J
Dong
Leying
L
Wen
Ye
Y
Zhang
Hongjie
H
Yu
Zijian
Z
Feng
Minmei
M
Chen
Yi
Y
Tan
Zhaojun
Z
Mo
Haiyan
H
Liu
Yunyan
Y
Fan
Kunxiong
K
Li
Chris Ka-Fai
CK
Li
Dexin
D
Li
Weizhong
W
Yang
Yuelong
Y
Shu
D000328:Adult; D017809:Fatal Outcome; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000302:isolation & purification; D007251:Influenza, Human / Q000235:genetics / Q000473:pathology / Q000821:virology*; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load