Sun Huizhen, Chang Le, Yan Ying, Ji Huimin, Jiang Xinyi, Song Shi, Xiao Yingzi, Lu Zhuoqun, Wang Lunan
National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, PR China; Beijing Engineering Research Center of Laboratory Medicine, Beijing, PR China; National Center for Clinical Laboratories, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, PR China.
National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, PR China; Beijing Engineering Research Center of Laboratory Medicine, Beijing, PR China.
Antiviral Res. 2022 Dec;208:105448. doi: 10.1016/j.antiviral.2022.105448. Epub 2022 Oct 17.
Occult hepatitis B virus (HBV) infection (OBI) has non-negligible clinical significance, but the mechanism of its occurrence remains unclear. Growing evidence suggests that mutations in the pre-S region of HBV genome may be associated with the occurrence of OBI. However, the role of pre-S mutations in OBI and its molecular mechanism was not fully understand. Here, the pre-S sequences from 307 OBI blood donors and 293 hepatitis B surface protein (HBsAg)-positive blood donors were obtained, and we observed a higher frequency of naturally occurring pre-S mutations in OBI donors infected with genotype B/C HBV than in HBsAg-positive donors, suggesting their potential positive role in OBI. In both genotype B and C, several pre-S mutants resulted in markedly reduced HBsAg production in vitro. In particular, the T68I, S78N and N98T mutants of genotype B were proven to significantly decrease the HBsAg synthesis by affecting the pre-S2/S promoter activity, and thereby promoting the occurrence of OBI.
隐匿性乙型肝炎病毒（HBV）感染（OBI）具有不可忽视的临床意义，但其发生机制仍不清楚。越来越多的证据表明，HBV基因组前S区的突变可能与OBI的发生有关。然而，前S区突变在OBI中的作用及其分子机制尚未完全明确。在此，我们获取了307名OBI献血者和293名乙型肝炎表面蛋白（HBsAg）阳性献血者的前S区序列，并且我们观察到，与HBsAg阳性献血者相比，感染B/C基因型HBV的OBI献血者中自然发生前S区突变的频率更高，这表明它们在OBI中可能具有积极作用。在B型和C型基因型中，几种前S区突变体在体外均导致HBsAg产生显著减少。特别是，B型基因型的T68I、S78N和N98T突变体被证明通过影响前S2/S启动子活性而显著降低HBsAg合成，从而促进OBI的发生。
