Worldwide increased prevalence of human adenovirus type 3 (HAdV-3) respiratory infections is well correlated with heterogeneous hypervariable regions (HVRs) of hexon.
Worldwide increased prevalence of human adenovirus type 3 (HAdV-3) respiratory infections is well correlated with heterogeneous hypervariable regions (HVRs) of hexon.
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DOI：
10.1371/journal.pone.0194516
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Adhikary AK
中科院分区：
文献类型：
--
作者：
Haque E;Banik U;Monowar T;Anthony L;Adhikary AK
人类腺病毒3（HADV-3）呼吸道感染发生在全世界的儿童和成人中，导致严重的发病率和死亡率，尤其是在儿科年龄组，尤其是在新生儿中。在HADV感染期间，对位于六链蛋白的超变量区域（HVR）的表位形成中和抗体。这些中和抗体可保护相同类型的病毒再感染。因此，可以合理地推测HVR中HADV-3的变化可能会损害先前感染所获得的免疫力，其HVR中有不同的菌株。 HADV-3最近已成为全球急性呼吸道感染的主要药物，造成了所有腺病毒呼吸道感染的15％至87％。然而，尽管HADV-3作为呼吸道病原体的患病率增加，但循环菌株中己酮蛋白的多样性仍未开发。这项研究旨在探索全球分布的HADV-3菌株中HEXON HVR的变化，并发现它们之间可能的关系，因此可能阐明了HADV-3患病率增加的原因。在这项研究中，我们首次分析了NCBI数据库中所有248种可用HADV-3菌株的Hexon蛋白，并将其与HADV-3原型（GB染色）的六个可用菌株进行了比较。我们发现，全世界循环的HADV -3菌株的HVR是高度异质性的，并且自从他们的原始隔离以来一直在不断突变。基于它们的巨大异质性，可以将菌株分为25种六链变体（3HV-1至3HV-25），其中4个（3HV-1至3HV-4）占菌株的80％。这种异质性可以解释为什么HADV-3已成为全球最普遍的HADV类型。己酮蛋白的异质性还表明，针对HADV-3的疫苗的开发可能具有挑战性。此处提供的有关己孔变体的数据可能对HADV-3感染的未来流行病学研究很有用。
Human adenovirus type 3 (HAdV-3) respiratory infections occurs worldwide in both children and adults, leading to severe morbidity and mortality, particularly in the paediatric age group and especially in neonates. During HAdV infection, neutralizing antibodies are formed against the epitopes located in the hyper variable regions (HVRs) of the hexon protein. These neutralizing antibodies provide protection against reinfection by viruses of the same type. Therefore it is reasonable to speculate that variations of HAdV-3 in the HVRs could impair the immunity acquired by previous infection with a different strain with variation in its HVRs. HAdV-3 has recently become the major agent of acute respiratory infection worldwide, being responsible for 15% to 87% of all adenoviral respiratory infections. However, despite the increased prevalence of HAdV-3 as respiratory pathogen, the diversity of hexon proteins in circulating strains remains unexplored. This study was designed to explore the variation in HVRs of hexon among globally distributed strains of HAdV-3 as well as to discover possible relationship among them, thus possibly shedding light on the cause for the increased prevalence of HAdV-3. In this study, for the first time we analysed the hexon proteins of all 248 available strains of HAdV-3 from the NCBI database and compared them with those of the HAdV-3 prototype (GB stain). We found that the HVRs of HAdV-3 strains circulating worldwide were highly heterogeneous and have been mutating continuously since -their original isolation. Based on their immense heterogeneity, the strains can be categorized into 25 hexon variants (3Hv-1 to 3Hv-25), 4 of which (3Hv-1 to 3Hv-4) comprises 80% of the strains. This heterogeneity may explain why HAdV-3 has become the most prevalent HAdVs type worldwide. The heterogeneity of hexon proteins also shows that the development of a vaccine against HAdV-3 might be challenging. The data on hexon variants provided here may be useful for the future epidemiological study of HAdV-3 infection.
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