Hu Xiao-Xiao, Ma Yan-Xiu, Lin Yao-Xiang, Wu Xiang-Ji, Wu Jing, Ma Hui, Lin Sheng-Zhang, Chen Gong-Yin, Pan Xiao-Ben
School of Basic Medicine, Key Laboratory of Inflammation and Immunoregulation of Hangzhou, Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
Peking University Health Center, People's Hospital, Peking University Hepatology Institute, Beijing 100044, China.
Infect Dis Immun. 2021 Apr 20;1(1):36-42. doi: 10.1097/ID9.0000000000000007. eCollection 2021 Apr.
Pre-existing liver disease is a risk factor for the worse prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to evaluate whether chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) affect the expression of viral receptor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in the liver.
Twelve pairs of matched liver tissues of HCC and para-carcinoma were collected from the First Affiliated Hospital of Zhejiang University School of Medicine. And 20 liver biopsies from CHB patients were collected from Peking University People's Hospital. The expression of ACE2 and TMRPSS2 were detected using immunofluorescence staining, western blot, and RT-qPCR. The effects of hepatitis B virus (HBV) replication or interferon on ACE2 and TMPRSS2 expression were tested in hepatic cell lines.
The mRNA expression of TMPRSS2 in HCC tissues was six-fold higher than that of para-carcinoma tissues ( = 0.002), whereas that of ACE2 was not statistically different between HCC and para-carcinoma tissues. Hepatocellular ACE2 expression was detected in 35% (7/20) of CHB patients and mostly distributed in the inflammatory areas. However, there was no difference in TMPRSS2 expression between areas with or without inflammation. IFN-α2b slightly induced ACE2 expression (2.4-fold, = 0.033) in HepG2 cells but not in Huh-7, QSG-7701, and L-02 cells. IFN-α2b did not affect TMPRSS2 expression in these cell lines. In addition, HBV replication did not alter ACE2 expression in HepAD38 cells.
Although HBV replication does not directly affect the expression of ACE2 and TMPRSS2, intrahepatic inflammation and carcinogenesis may increase their expression in some patients, which, in turn, may facilitate SARS-CoV-2 infection in hepatocytes.
既往存在的肝脏疾病是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染预后较差的一个危险因素。我们旨在评估慢性乙型肝炎（CHB）和肝细胞癌（HCC）是否会影响肝脏中病毒受体血管紧张素转换酶2（ACE2）和跨膜丝氨酸蛋白酶2（TMPRSS2）的表达。
从浙江大学医学院附属第一医院收集了12对匹配的HCC及癌旁肝脏组织。从北京大学人民医院收集了20例CHB患者的肝脏活检组织。采用免疫荧光染色、蛋白质印迹法和逆转录定量聚合酶链反应（RT-qPCR）检测ACE2和TMPRSS2的表达。在肝细胞系中检测乙型肝炎病毒（HBV）复制或干扰素对ACE2和TMPRSS2表达的影响。
HCC组织中TMPRSS2的mRNA表达比癌旁组织高6倍（P = 0.002），而HCC与癌旁组织中ACE2的mRNA表达无统计学差异。在35%（7/20）的CHB患者中检测到肝细胞ACE2表达，且大多分布于炎症区域。然而，有炎症和无炎症区域的TMPRSS2表达无差异。干扰素-α2b在HepG2细胞中轻微诱导ACE2表达（2.4倍，P = 0.033），但在Huh-7、QSG-7701和L-02细胞中未诱导。干扰素-α2b不影响这些细胞系中TMPRSS2的表达。此外，HBV复制未改变HepAD38细胞中ACE2的表达。
虽然HBV复制不直接影响ACE2和TMPRSS2的表达，但肝内炎症和致癌作用可能会增加部分患者中它们的表达，进而可能促进SARS-CoV-2在肝细胞中的感染。
