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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.02188

The underlying mechanism of 3-hydroxyphthalic anhydride-modified bovine beta-lactoglobulin to block human papillomavirus entry into the host cell

  • 1Fudan University, China
  • 2Chinese Academy of Sciences, China

We have previously demonstrated that 3-hydroxyphthalic anhydride (3HP)- modified bovine beta-lactoglobulin (3HP-β-LG) is highly effective in inhibiting in vitro infection by pseudovirus (PsV) of high- and low-risk human papillomavirus (HPV). Intravaginally applied 3HP-β-LG-containing vaginal gel could significantly inhibit HPV infection and reduce viral load in the cervical region. However, we still do not understand the underlying molecular mechanism by which 3HP-β-LG is able to inhibit HPV infection. Here, though, we showed that 3HP-β-LG did not inactivate HPV PsV, but rather blocked entry of HPV PsV into the target cell via its interaction with virus, not cell. It bound to the positively charged region in the HPV L1 protein, suggesting that 3HP-β-LG binds to HPV L1 protein through the interaction between the negatively charged region in 3HP-β-LG and the positively charged region in HPV L1 protein, thus competitively blocking the binding of HPV to the receptor on the basement membrane in vaginal mucosa. Although 3HP-modified chicken ovalbumin (3HP-OVA) also carries high net negative charges, it exhibited no anti-HPV activity, suggesting that the interaction between 3HP-modified protein and HPV L1 protein relies on both electrostatic and matchable conformation of the binding sites in both proteins. When topically applied, 3HP-β-LG did not enter the host cell or blood circulation.These findings suggest that 3HP-β-LG targets HPV L1 protein and blocks HPV entry into the host cell, thus being safe and effective for topical application in the treatment of HPV infection.

Keywords: 3HP-β-LG, HPV – human papillomavirus, entry inhibitor, L1 protein, negatively charged protein

Received: 13 Jul 2019; Accepted: 05 Sep 2019.

Copyright: © 2019 Hua, Zhu, Wu, Si, Wang, Sui and Shibo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Yun Zhu, Chinese Academy of Sciences, Beijing, 100864, Beijing, China, zhuyun@ibp.ac.cn
Mx. Long Sui, Fudan University, Shanghai, 200433, Shanghai Municipality, China, suilong@fudan.edu.cn
Prof. Jiang Shibo, Fudan University, Shanghai, 200433, Shanghai Municipality, China, shibojiang@fudan.edu.cn