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Inhibition of in vitro Infection of Hepatitis B Virus by Human Breastmilk

22 Pages Posted: 13 Apr 2021

See all articles by Yuqian Luo

Yuqian Luo

Nanjing University - Jiangsu Key Laboratory for Molecular Medicine

Kuanhui Xiang

Peking University - Department of Microbiology and Infectious Disease

Jingli Liu

Nanjing University - Jiangsu Key Laboratory of Molecular Medicine

Ji Song

Peking University - Department of Microbiology and Infectious Disease

Jing Feng

Nanjing University - Drum Tower Hospital, Department of Obstetrics and Gynecology

Jie Chen

Nanjing University - Drum Tower Hospital, Department of Obstetrics and Gynecology

Yimin Dai

Nanjing University - Drum Tower Hospital, Department of Obstetrics and Gynecology

Yali Hu

Nanjing University - Center for Reproductive Medicine; Nanjing University - Drum Tower Hospital, Department of Obstetrics and Gynecology

Hui Zhaung

Peking University - Department of Microbiology and Infectious Disease

Yi-Hua Zhou

Nanjing University - Jiangsu Key Laboratory for Molecular Medicine; Nanjing University - Department of Biostatistics; Nanjing University - Department of Laboratory Medicine and Infectious Diseases

More...

Abstract

Background: Despite the presence of hepatitis B virus (HBV) in human breastmilk of mothers infected with HBV, breastfeeding does not increase the risk of mother-to-child transmission (MTCT) of HBV. We hypothesized that human breastmilk may contain active component(s) that binds to HBV and inhibits the infectivity of HBV.

Methods: Competitive inhibition immunoassays and far-Western blotting were used to test the binding of human whey to hepatitis B surface antigen (HBsAg). The identity of the component(s) responsible for the binding was determined by protein mass spectrometry. The inhibition of human whey and binding component on the infectivity of HBV was evaluated in an HBV culture system based on HepG2 cells that stably express sodium-taurocholate co-transporter polypeptide (NTCP).

Results: Human whey significantly inhibited the binding of HBsAg to anti-HBs in competitive inhibition immunoassays. The far-Western blotting showed that HBsAg bound to a protein at approximately 80 kD, which was identified to be lactoferrin by mass spectrometry. Competitive inhibition immunoassays further demonstrated that human and bovine lactoferrin bound to HBsAg. Human whey from HBsAg-negative or -positive mothers, natural human lactoferrin, recombinant human lactoferrin, and bovine lactoferrin each significantly inhibited the infectivity of HBV in HepG2-NTCP cells.

Interpretation: Our results indicate that human breastmilk can bind to HBsAg and inhibit the infectivity of HBV and the active component is lactoferrin. The findings may explain the reason that breastfeeding has no additional risk for MTCT of HBV, although human breastmilk contains HBV.

Funding Information: National Natural Science Foundation of China (81672002), the Science and Technology Department of Jiangsu Province (BK20161105), and the Jiangsu Provincial Department of Health (H201537), China.

Declaration of Interests: The authors who have taken part in this study declared that they do not have anything to disclose regarding conflict of interest with respect to this manuscript.

Ethics Approval Statement: This study was approved by the institutional review boards of Nanjing Drum Tower Hospital.

Keywords: human breastmilk, lactoferrin, HBsAg-binding protein, inhibition of infectivity of hepatitis B virus

Suggested Citation

Luo, Yuqian and Xiang, Kuanhui and Liu, Jingli and Song, Ji and Feng, Jing and Chen, Jie and Dai, Yimin and Hu, Yali and Hu, Yali and Zhaung, Hui and Zhou, Yi-Hua, Inhibition of in vitro Infection of Hepatitis B Virus by Human Breastmilk. Available at SSRN: https://ssrn.com/abstract=3825513 or http://dx.doi.org/10.2139/ssrn.3825513

Yuqian Luo

Nanjing University - Jiangsu Key Laboratory for Molecular Medicine ( email )

China

Kuanhui Xiang

Peking University - Department of Microbiology and Infectious Disease ( email )

Beijing, 100191
China

Jingli Liu

Nanjing University - Jiangsu Key Laboratory of Molecular Medicine

Nanjing, 210093
China

Ji Song

Peking University - Department of Microbiology and Infectious Disease

Beijing, 100191
China

Jing Feng

Nanjing University - Drum Tower Hospital, Department of Obstetrics and Gynecology

321 Zhong Shan Road
Nanjing, Jiangning District 210008
China

Jie Chen

Nanjing University - Drum Tower Hospital, Department of Obstetrics and Gynecology

321 Zhong Shan Road
Nanjing, Jiangning District 210008
China

Yimin Dai

Nanjing University - Drum Tower Hospital, Department of Obstetrics and Gynecology

321 Zhong Shan Road
Nanjing, Jiangning District 210008
China

Yali Hu

Nanjing University - Drum Tower Hospital, Department of Obstetrics and Gynecology ( email )

China

Nanjing University - Center for Reproductive Medicine ( email )

Nanjing
China

Hui Zhaung

Peking University - Department of Microbiology and Infectious Disease ( email )

China

Yi-Hua Zhou (Contact Author)

Nanjing University - Jiangsu Key Laboratory for Molecular Medicine ( email )

China

Nanjing University - Department of Biostatistics ( email )

China

Nanjing University - Department of Laboratory Medicine and Infectious Diseases ( email )

Nanjing
China