The inhibitory effects and mechanisms of polymannuroguluronate sulfate against human papillomavirus infection in vitro and in vivo

摘要

Human papillomaviruses (HPVs) are non-enveloped DNA viruses that infect epithelia and can cause a wide variety of benign and pre-malignant epithelial tumours. The sulfated polysaccharides such as carrageenans were reported to be able to interfere with the binding process of HPV to the cell surface. In this study, brown seaweed derived polysaccharides polymannuroguluronate sulfate (PMGS) were prepared, and their anti-HPV effects were explored in vitro and in vivo. The results indicated that PMGS effectively inhibited high-risk HPV16 and HPV45 infection with very low toxicity. PMGS may inactivate HPV particles or block the binding and entry process of HPV through direct interaction with viral capsid proteins. PMGS can enter into HeLa cells and down-regulate the expression levels of viral oncogene proteins E6 and E7. In addition, PMGS also dramatically inhibited HPV infection on the skin of BALB/c Nude Mice. Thus, marine derived polysaccharide PMGS possessed anti-HPV activities in vitro and in vivo, and may block HPV infection via targeting viral capsid L1 protein, suggesting that it has great potential to be developed into a novel anti-HPV agent in the future.