Molecular pathology analyses of two fatal human infections of avian influenza A(H7N9) virus

被引:20
作者
Feng, Yanling [1 ]
Hu, Lvyin [2 ]
Lu, Shuihua [3 ]
Chen, Qingguo [3 ]
Zheng, Ye [1 ]
Zeng, Dong [1 ]
Zhang, Jun [2 ]
Zhang, Anli [4 ]
Chen, Liang [5 ]
Hu, Yunwen [6 ]
Zhang, Zhiyong [7 ]
机构
[1] Fudan Univ, Dept Pathol, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China
[2] Fudan Univ, Dept Clin Lab, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China
[3] Fudan Univ, Dept Resp Med, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China
[4] Fudan Univ, Sci Res Ctr, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China
[5] Fudan Univ, Dept Viral Hepatitis, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China
[6] Fudan Univ, Dept Pathogen Diag & Biosafety, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China
[7] Fudan Univ, Dept Radiol, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China
基金
中国国家自然科学基金;
关键词
A H7N9 VIRUS; SURFACTANT PROTEIN-A; COMPLEMENT;
D O I
10.1136/jclinpath-2014-202441
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Aims To investigate the histopathological manifestations of two fatal cases of H7N9 influenza A virus infection. Methods Pulmonary and hepatic specimens from two fatal cases of H7N9 influenza virus infection were examined using H&E staining. Additionally, in situ hybridisation was performed with probes (ViewRNA) targeting H7N9 RNA and IP-10, interleukin (IL)-6 mRNA. The distribution of surfactant protein A (SP-A), surfactant protein B (SP-B), CD3, CD4, CD8, CD68 and C4d were determined with immunohistochemistry. Results Apart from the typical diffuse alveolar damage and hyaline membrane observed in severe influenza infection, we detected H7N9 RNA and massive intrapulmonary production of IP-10 and IL-6 mRNA using in situ hybridisation. Hyperplasia of type II pneumocytes was observed by H&E staining and immunohistochemistry. Proliferating macrophages and clustered neutrophils in the infected lungs were observed, whereas T lymphocytes, especially CD4T helper cells, were markedly depleted. No obvious complement deposition was found in lung tissues. Conclusions Our findings suggest that H7N9 influenza virus induced an immunological response towards overt pulmonary inflammation and systemic lymphopenia which led to intense alveolar damage and respiratory failure.
引用
收藏
页码:57 / 63
页数:7
相关论文
共 21 条
[1]   Serologic Study for Influenza A (H7N9) among High-Risk Groups in China [J].
Bai, Tian ;
Zhou, Jianfang ;
Shu, Yuelong .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (24) :2339-+
[2]   INTERACTIONS OF SURFACTANT PROTEIN-A WITH INFLUENZA-A VIRUSES - BINDING AND NEUTRALIZATION [J].
BENNE, CA ;
KRAAIJEVELD, CA ;
VANSTRIJP, JAG ;
BROUWER, E ;
HARMSEN, M ;
VERHOEF, J ;
VANGOLDE, LMG ;
VANIWAARDEN, JF .
JOURNAL OF INFECTIOUS DISEASES, 1995, 171 (02) :335-341
[3]   Cytokine and Chemokine Levels in Patients Infected With the Novel Avian Influenza A (H7N9) Virus in China [J].
Chi, Ying ;
Zhu, Yefei ;
Wen, Tian ;
Cui, Lunbiao ;
Ge, Yiyue ;
Jiao, Yongjun ;
Wu, Tao ;
Ge, Aihua ;
Ji, Hong ;
Xu, Ke ;
Bao, Changjun ;
Zhu, Zheng ;
Qi, Xian ;
Wu, Bin ;
Shi, Zhiyang ;
Tang, Fenyang ;
Xing, Zheng ;
Zhou, Minghao .
JOURNAL OF INFECTIOUS DISEASES, 2013, 208 (12) :1962-1967
[4]   Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes [J].
Clara Monsalvo, Ana ;
Batalle, Juan P. ;
Florencia Lopez, M. ;
Krause, Jens C. ;
Klemenc, Jennifer ;
Zea Hernandez, Johanna ;
Maskin, Bernardo ;
Bugna, Jimena ;
Rubinstein, Carlos ;
Aguilar, Leandro ;
Dalurzo, Liliana ;
Libster, Romina ;
Savy, Vilma ;
Baumeister, Elsa ;
Aguilar, Liliana ;
Cabral, Graciela ;
Font, Julia ;
Solari, Liliana ;
Weller, Kevin P. ;
Johnson, Joyce ;
Echavarria, Marcela ;
Edwards, Kathryn M. ;
Chappell, James D. ;
Crowe, James E., Jr. ;
Williams, John V. ;
Melendi, Guillermina A. ;
Polack, Fernando P. .
NATURE MEDICINE, 2011, 17 (02) :195-U225
[5]   Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia [J].
de Jong, Menno D. ;
Simmons, Cameron P. ;
Thanh, Tran Tan ;
Hien, Vo Minh ;
Smith, Gavin J. D. ;
Chau, Tran Nguyen Bich ;
Hoang, Dang Minh ;
Chau, Nguyen Van Vinh ;
Khanh, Truong Huu ;
Dong, Vo Cong ;
Qui, Phan Tu ;
Van Cam, Bach ;
Ha, Do Quang ;
Guan, Yi ;
Peiris, J. S. Malik ;
Chinh, Nguyen Tran ;
Hien, Tran Tinh ;
Farrar, Jeremy .
NATURE MEDICINE, 2006, 12 (10) :1203-1207
[6]   Clinical Findings in 111 Cases of Influenza A (H7N9) Virus Infection [J].
Gao, Hai-Nv ;
Lu, Hong-Zhou ;
Cao, Bin ;
Du, Bin ;
Shang, Hong ;
Gan, Jian-He ;
Lu, Shui-Hua ;
Yang, Yi-Da ;
Fang, Qiang ;
Shen, Yin-Zhong ;
Xi, Xiu-Ming ;
Gu, Qin ;
Zhou, Xian-Mei ;
Qu, Hong-Ping ;
Yan, Zheng ;
Li, Fang-Ming ;
Zhao, Wei ;
Gao, Zhan-Cheng ;
Wang, Guang-Fa ;
Ruan, Ling-Xiang ;
Wang, Wei-Hong ;
Ye, Jun ;
Cao, Hui-Fang ;
Li, Xing-Wang ;
Zhang, Wen-Hong ;
Fang, Xu-Chen ;
He, Jian ;
Liang, Wei-Feng ;
Xie, Juan ;
Zeng, Mei ;
Wu, Xian-Zheng ;
Li, Jun ;
Xia, Qi ;
Jin, Zhao-Chen ;
Chen, Qi ;
Tang, Chao ;
Zhang, Zhi-Yong ;
Hou, Bao-Min ;
Feng, Zhi-Xian ;
Sheng, Ji-Fang ;
Zhong, Nan-Shan ;
Li, Lan-Juan .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (24) :2277-2285
[7]   Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus [J].
Gao, Rongbao ;
Cao, Bin ;
Hu, Yunwen ;
Feng, Zijian ;
Wang, Dayan ;
Hu, Wanfu ;
Chen, Jian ;
Jie, Zhijun ;
Qiu, Haibo ;
Xu, Ke ;
Xu, Xuewei ;
Lu, Hongzhou ;
Zhu, Wenfei ;
Gao, Zhancheng ;
Xiang, Nijuan ;
Shen, Yinzhong ;
He, Zebao ;
Gu, Yong ;
Zhang, Zhiyong ;
Yang, Yi ;
Zhao, Xiang ;
Zhou, Lei ;
Li, Xiaodan ;
Zou, Shumei ;
Zhang, Ye ;
Li, Xiyan ;
Yang, Lei ;
Guo, Junfeng ;
Dong, Jie ;
Li, Qun ;
Dong, Libo ;
Zhu, Yun ;
Bai, Tian ;
Wang, Shiwen ;
Hao, Pei ;
Yang, Weizhong ;
Zhang, Yanping ;
Han, Jun ;
Yu, Hongjie ;
Li, Dexin ;
Gao, George F. ;
Wu, Guizhen ;
Wang, Yu ;
Yuan, Zhenghong ;
Shu, Yuelong .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (20) :1888-1897
[8]   H5N1 infection of the respiratory tract and beyond: a molecular pathology study [J].
Gu, Jiang ;
Xie, Zhigang ;
Gao, Zhancheng ;
Liu, Jinhua ;
Korteweg, Christine ;
Ye, Juxiang ;
Lau, Lok Ting ;
Lu, Jie ;
Gao, Zifen ;
Zhang, Bo ;
McNutt, Michael A. ;
Lu, Min ;
Anderson, Virginia M. ;
Gong, Encong ;
Yu, Albert Cheung Hoi ;
Lipkin, W. Ian .
LANCET, 2007, 370 (9593) :1137-1145
[9]   Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance [J].
Hu, Yunwen ;
Lu, Shuihua ;
Song, Zhigang ;
Wang, Wei ;
Hao, Pei ;
Li, Jianhua ;
Zhang, Xiaonan ;
Yen, Hui-Ling ;
Shi, Bisheng ;
Li, Tao ;
Guan, Wencai ;
Xu, Lei ;
Liu, Yi ;
Wang, Sen ;
Zhang, Xiaoling ;
Tian, Di ;
Zhu, Zhaoqin ;
He, Jing ;
Huang, Kai ;
Chen, Huijie ;
Zheng, Lulu ;
Li, Xuan ;
Ping, Jie ;
Kang, Bin ;
Xi, Xiuhong ;
Zha, Lijun ;
Li, Yixue ;
Zhang, Zhiyong ;
Peiris, Malik ;
Yuan, Zhenghong .
LANCET, 2013, 381 (9885) :2273-2279
[10]   Surfactant protein A (SP-A): the alveolus and beyond [J].
Khubchandani, KR ;
Snyder, JM .
FASEB JOURNAL, 2001, 15 (01) :59-69