Zhang Guangzhi, Bashiri Kiandokht, Kneteman Mark, Cave Kevan, Hong Youngkee, Mackey John R, Alter Harvey J, Mason Andrew L
Center of Excellence for Gastrointestinal Inflammation and Immunity Research, Division of Gastroenterology, University of Alberta, Edmonton, AB T6G 2E1, Canada.
National Microbiology Laboratory, Winnipeg, MB R3E 3M4, Canada.
J Oncol. 2020 Jan 27;2020:8958192. doi: 10.1155/2020/8958192. eCollection 2020.
Mouse mammary tumor virus (MMTV) is a betaretrovirus that plays a causal role in the development of breast cancer and lymphoma in mice. Closely related sequences that share 91-99% nucleotide identity with MMTV have been repeatedly found in humans with neoplastic and inflammatory diseases. Evidence for infection with a betaretrovirus has been found in patients with breast cancer and primary biliary cholangitis and referred to as the human mammary tumor virus and the human betaretrovirus (HBRV), respectively. Using the gold standard technique of demonstrating retroviral infection, HBRV proviral integrations have been detected in cholangiocytes, lymph nodes, and liver of patients with primary biliary cholangitis. However, the scientific biomedical community has not embraced the hypothesis that MMTV like betaretroviruses may infect humans because reports of viral detection have been inconsistent and robust diagnostic assays are lacking. Specifically, prior serological assays using MMTV proteins have produced divergent results in human disease. Accordingly, a partial HBRV surface (Su) construct was transfected into HEK293 to create an ELISA. The secreted HBRV gp52 Su protein was then used to screen for serological responses in patients with breast cancer and liver disease. A greater proportion of breast cancer patients ( = 98) were found to have serological reactivity to HBRV Su as compared to age- and sex-matched control subjects (10.2% versus 2.0%, =0.017, OR = 5.6 [1.25-26.3]). Similarly, the frequency of HBRV Su reactivity was higher in patients with primary biliary cholangitis ( = 156) as compared to blood donors (11.5% vs. 3.1%, =0.0024, OR = 4.09 [1.66-10.1]). While the sensitivity of the HBRV Su ELISA was limited, the assay was highly specific for serologic detection in patients with breast cancer or primary biliary cholangitis, respectively (98.0% [93.1%-99.7%] and 97.0% [93.4%-98.6%]). Additional assays will be required to link immune response to betaretrovirus infection and either breast cancer or primary biliary cholangitis.
小鼠乳腺肿瘤病毒（MMTV）是一种β逆转录病毒，在小鼠乳腺癌和淋巴瘤的发生中起因果作用。在患有肿瘤性和炎症性疾病的人类中，反复发现了与MMTV具有91-99%核苷酸同一性的密切相关序列。在乳腺癌和原发性胆汁性胆管炎患者中发现了感染β逆转录病毒的证据，分别称为人类乳腺肿瘤病毒和人类β逆转录病毒（HBRV）。使用证明逆转录病毒感染的金标准技术，在原发性胆汁性胆管炎患者的胆管细胞、淋巴结和肝脏中检测到了HBRV前病毒整合。然而，科学的生物医学界尚未接受MMTV样β逆转录病毒可能感染人类的假说，因为病毒检测报告不一致且缺乏可靠的诊断检测方法。具体而言，先前使用MMTV蛋白的血清学检测在人类疾病中产生了不同的结果。因此，将部分HBRV表面（Su）构建体转染到HEK293中以创建一种酶联免疫吸附测定（ELISA）。然后使用分泌的HBRV gp52 Su蛋白筛选乳腺癌和肝病患者的血清学反应。与年龄和性别匹配的对照受试者相比，发现更大比例的乳腺癌患者（n = 98）对HBRV Su有血清学反应（10.2%对2.0%，P = 0.017，OR = 5.6 [1.25 - 26.3]）。同样，与献血者相比，原发性胆汁性胆管炎患者（n = 156）中HBRV Su反应性的频率更高（11.5%对3.1%，P = 0.0024，OR = 4.09 [1.66 - 10.1]）。虽然HBRV Su ELISA的敏感性有限，但该检测方法分别对乳腺癌或原发性胆汁性胆管炎患者的血清学检测具有高度特异性（98.0% [93.1% - 99.7%]和97.0% [93.4% - 98.6%]）。需要额外的检测来将免疫反应与β逆转录病毒感染以及乳腺癌或原发性胆汁性胆管炎联系起来。
