Human herpesvirus diversity is altered in HLA class I binding peptides.
Human herpesvirus diversity is altered in HLA class I binding peptides.
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人类疱疹病毒的多样性在HLA I类结合肽中改变。
DOI：
10.1073/pnas.2123248119
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发表时间：
2022-05-03
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
病毒进化以逃避免疫识别，否则可能会限制传播。人类白细胞抗原（HLA）I类呈递病毒肽是免疫细胞识别感染的必要步骤。逃避这种免疫识别的病毒适应性尚未在HLA I类同种异型和病毒株的多样性中进行正式测试。我们分析了三种人类疱疹病毒的遗传多样性，结合不同的HLA I类同种异型肽。我们发现，适应逃避HLA I类识别可能是一个普遍的现象，塑造人类疱疹病毒的遗传多样性，特别是那些蛋白质在病毒潜伏期。这种广泛的范围，跨越人类和病毒的多样性，提供了一个独特的比较视角的人类疱疹病毒的共同进化。疱疹病毒是普遍存在的遗传多样性DNA病毒，在人类中长期存在，与罕见但显著的病理学相关。人类白细胞抗原（HLA）I类将来自感染组织细胞的细胞内衍生肽片段呈递给CD 8 + T细胞和自然杀伤细胞，从而指导抗病毒免疫。高度多态性的HLA I类的同种异型通过其肽结合库来区分。由于这种HLA I类变异是疱疹病毒疾病的主要决定因素，我们研究了病毒蛋白的序列多样性是否反映了HLA呈递的逃避。使用EB病毒（EBV）、人巨细胞病毒（HCMV）和水痘-带状疱疹病毒的群体基因组数据，我们测试了疱疹病毒蛋白质区域之间的多样性是否存在差异，这些区域是否可以被HLA I类识别。疱疹病毒表现出裂解和潜伏感染阶段，后者更好地使免疫逃避。尽管裂解蛋白的HLA结合肽是保守的，但我们发现潜伏期期间表达的EBV和HCMV蛋白具有增加的肽序列多样性。类似地，潜伏的但不是裂解的疱疹病毒蛋白在HLA结合中比非结合肽具有更大的群体结构。最后，我们发现了与EBV适应当地HLA环境相一致的模式，高频HLA I类同种异型对EBV分离株的识别效率较低。在这里，CD 8 + T细胞表位的频率与HLA I类识别的频率呈负相关。以前的分析表明，病原体介导的自然选择保持特殊的多态性，决定肽识别的HLA残基。在这里，我们表明，HLA I类肽识别影响全球广泛分布的病原体的多样性。
Viruses evolve to evade immune recognition that may otherwise limit transmission. Presentation of virus peptides by human leukocyte antigen (HLA) class I is a necessary step in the recognition of infection by immune cells. Virus adaptation to evade this immune recognition has not been formally tested across the diversity of HLA class I allotypes and virus strains. We analyzed genetic diversity of three human herpesviruses across peptides that bind diverse HLA class I allotypes. We find that adaptation to evade HLA class I recognition may be a general phenomenon shaping human herpesvirus genetic diversity, particularly for those proteins expressed during viral latency. This broad scope, across human and virus diversity, provides a unique comparative perspective of human–herpesvirus coevolution. Herpesviruses are ubiquitous, genetically diverse DNA viruses, with long-term presence in humans associated with infrequent but significant pathology. Human leukocyte antigen (HLA) class I presents intracellularly derived peptide fragments from infected tissue cells to CD8+ T and natural killer cells, thereby directing antiviral immunity. Allotypes of highly polymorphic HLA class I are distinguished by their peptide binding repertoires. Because this HLA class I variation is a major determinant of herpesvirus disease, we examined if sequence diversity of virus proteins reflects evasion of HLA presentation. Using population genomic data from Epstein–Barr virus (EBV), human cytomegalovirus (HCMV), and Varicella–Zoster virus, we tested whether diversity differed between the regions of herpesvirus proteins that can be recognized, or not, by HLA class I. Herpesviruses exhibit lytic and latent infection stages, with the latter better enabling immune evasion. Whereas HLA binding peptides of lytic proteins are conserved, we found that EBV and HCMV proteins expressed during latency have increased peptide sequence diversity. Similarly, latent, but not lytic, herpesvirus proteins have greater population structure in HLA binding than nonbinding peptides. Finally, we found patterns consistent with EBV adaption to the local HLA environment, with less efficient recognition of EBV isolates by high-frequency HLA class I allotypes. Here, the frequency of CD8+ T cell epitopes inversely correlated with the frequency of HLA class I recognition. Previous analyses have shown that pathogen-mediated natural selection maintains exceptional polymorphism in HLA residues that determine peptide recognition. Here, we show that HLA class I peptide recognition impacts diversity of globally widespread pathogens.
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影响因子：
6.7
作者：
Bristol JA;Djavadian R;Albright ER;Coleman CB;Ohashi M;Hayes M;Romero-Masters JC;Barlow EA;Farrell PJ;Rochford R;Kalejta RF;Johannsen EC;Kenney SC
通讯作者：
Kenney SC
影响因子：
5.2
作者：
Cruz-Muñoz ME;Fuentes-Pananá EM
通讯作者：
Fuentes-Pananá EM
DOI：
10.3390/v13061172
发表时间：
2021-06-18
期刊：
Viruses
影响因子：
--
作者：
Blazquez AC;Berenstein AJ;Torres C;Izquierdo A;Lezama C;Moscatelli G;De Matteo EN;Lorenzetti MA;Preciado MV
通讯作者：
Preciado MV
DOI：
10.1073/pnas.1818130116
发表时间：
2019-03-19
影响因子：
11.1
作者：
Cudini, Juliana;Roy, Sunando;Breuer, Judith
通讯作者：
Breuer, Judith
影响因子：
30.8
作者：
Bei, Jin-Xin;Li, Yi;Zeng, Yi-Xin
通讯作者：
Zeng, Yi-Xin