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Deep mutational scanning of SARS-CoV-2 Omicron BA.2.86 and epistatic emergence of the KP.3 variant SARS-CoV-2 Omicron BA.2.86 的深度突变扫描和 KP.3 变异的表观出现
IF 5.3 2区 医学 Q1 VIROLOGY Pub Date : 2024-09-02 DOI: 10.1093/ve/veae067
Ashley L Taylor, Tyler N Starr
Deep mutational scanning experiments aid in the surveillance and forecasting of viral evolution by providing prospective measurements of mutational effects on viral traits, but epistatic shifts in the impacts of mutations can hinder viral forecasting when measurements were made in outdated strain backgrounds. Here, we report measurements of the impact of all single amino acid mutations on ACE2-binding affinity and protein folding and expression in the SARS-CoV-2 Omicron BA.2.86 spike receptor-binding domain (RBD). As with other SARS-CoV-2 variants, we find a plastic and evolvable basis for receptor binding, with many mutations at the ACE2 interface maintaining or even improving ACE2-binding affinity. Despite its large genetic divergence, mutational effects in BA.2.86 have not diverged greatly from those measured in its Omicron BA.2 ancestor. However, we do identify strong positive epistasis among subsequent mutations that have accrued in BA.2.86 descendants. Specifically, the Q493E mutation that decreased ACE2-binding affinity in all previous SARS-CoV-2 backgrounds is reversed in sign to enhance human ACE2-binding affinity when coupled with L455S and F456L in the currently emerging KP.3 variant. Our results point to a modest degree of epistatic drift in mutational effects during recent SARS-CoV-2 evolution but highlight how these small epistatic shifts can have important consequences for the emergence of new SARS-CoV-2 variants.
深度突变扫描实验通过前瞻性地测量突变对病毒性状的影响,有助于监测和预测病毒的进化,但在过时的毒株背景下进行测量时,突变影响的表观转移会阻碍病毒的预测。在这里,我们报告了所有单氨基酸突变对 SARS-CoV-2 Omicron BA.2.86 穗状受体结合域(RBD)中 ACE2 结合亲和力和蛋白质折叠及表达的影响的测量结果。与其他 SARS-CoV-2 变体一样,我们发现受体结合有一个可塑性和可进化的基础,ACE2 界面上的许多突变都能保持甚至提高 ACE2 的结合亲和力。尽管遗传差异很大,BA.2.86 的突变效应与其祖先 Omicron BA.2 的突变效应差异不大。不过,我们确实在 BA.2.86 后代中发现了后续突变之间的强正外显性。具体来说,Q493E 突变降低了之前所有 SARS-CoV-2 基因背景中 ACE2 的结合亲和力,但当与目前新出现的 KP.3 变异株中的 L455S 和 F456L 结合时,该突变却反向增强了人类 ACE2 的结合亲和力。我们的研究结果表明,在最近的SARS-CoV-2进化过程中,突变效应出现了一定程度的表观漂移,但同时也强调了这些微小的表观变化如何对SARS-CoV-2新变种的出现产生重要影响。
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引用次数: 0
SARS-CoV-2 Variant Replacement Constrains Vaccine-Specific Viral Diversification SARS-CoV-2 变异替换制约疫苗特异性病毒多样化
IF 5.3 2区 医学 Q1 VIROLOGY Pub Date : 2024-09-02 DOI: 10.1093/ve/veae071
Bethany L Dearlove, Anthony C Fries, Nusrat J Epsi, Stephanie A Richard, Anuradha Ganesan, Nikhil Huprikar, David A Lindholm, Katrin Mende, Rhonda E Colombo, Christopher Colombo, Hongjun Bai, Derek T Larson, Evan C Ewers, Tahaniyat Lalani, Alfred G Smith, Catherine M Berjohn, Ryan C Maves, Milissa U Jones, David Saunders, Carlos J Maldonado, Rupal M Mody, Samantha E Bazan, David R Tribble, Timothy Burgess, Mark P Simons, Brian K Agan, Simon D Pollett, Morgane Rolland
Background COVID-19 vaccine breakthrough infections have been important for all circulating SARS-CoV-2 variant periods, but the contribution of vaccine specific SARS-CoV-2 viral diversification to vaccine failure remains unclear. Methods This study analysed 595 SARS-CoV-2 sequences collected from Military Health System beneficiaries between December 2020 and April 2022 to investigate the impact of vaccination on viral diversity. Results By comparing sequences based on the vaccination status of the participant, we found limited evidence indicating that vaccination was associated with increased viral diversity in the SARS-CoV-2 spike, and we show little to no evidence of a substantial sieve effect within major variants; rather we show that rapid variant replacement constrained intra-genotype COVID-19 vaccine strain immune escape. Conclusions These data suggest that, during past and perhaps future periods of rapid SARS-CoV-2 variant replacement, vaccine-mediated effects were subsumed with other drivers of viral diversity due to the massive scale of infections and vaccinations that occurred in a short time frame. However, our results also highlight some limitations of using sieve analysis methods outside of placebo-controlled clinical trials.
背景 COVID-19 疫苗突破性感染对所有流行的 SARS-CoV-2 变异期都很重要,但疫苗特异性 SARS-CoV-2 病毒多样化对疫苗失败的贡献仍不清楚。方法 本研究分析了 2020 年 12 月至 2022 年 4 月期间从军队卫生系统受益者中收集的 595 个 SARS-CoV-2 序列,以研究接种疫苗对病毒多样性的影响。结果 通过比较基于参与者疫苗接种状态的序列,我们发现了有限的证据表明疫苗接种与 SARS-CoV-2 穗状病毒多样性的增加有关,而且我们几乎没有证据表明主要变异中存在实质性的筛网效应;相反,我们表明快速的变异替换限制了基因型内 COVID-19 疫苗株的免疫逃逸。结论 这些数据表明,在过去以及未来的 SARS-CoV-2 变异株快速替换期间,由于短时间内发生了大规模的感染和疫苗接种,疫苗介导的效应被病毒多样性的其他驱动因素所掩盖。不过,我们的研究结果也凸显了在安慰剂对照临床试验之外使用筛析方法的一些局限性。
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引用次数: 0
Phylogenetic evidence of extensive spatial mixing of diverse HIV-1 group M lineages within Cameroon but not between its neighbours 有系统发生学证据表明,喀麦隆境内存在多种多样的 HIV-1 M 族系的广泛空间混合,但其邻国之间并不存在这种混合
IF 5.3 2区 医学 Q1 VIROLOGY Pub Date : 2024-09-02 DOI: 10.1093/ve/veae070
Célestin Godwe, Oumarou H Goni, James E San, Nelson Sonela, Mérimé Tchakoute, Aubin Nanfack, Francioli K Koro, Christelle Butel, Nicole Vidal, Ralf Duerr, Darren P Martin, Tulio de Oliveira, Martine Peeters, Marcus Altfeld, Ahidjo Ayouba, Thumbi Ndung’u, Marcel Tongo
From the perspective of developing relevant interventions for treating HIV and controlling its spread, it is particularly important to comprehensively understand the underlying diversity of the virus; especially in countries where the virus has been present and evolving since the cross-species transmission event that triggered the global pandemic. Here we generate and phylogenetically analyse sequences derived from the gag-protease (2010 bp; n=115), partial integrase (345 bp; n=36), and nef (719 bp; n=321) genes of HIV-1 group M (HIV-1M) isolates sampled between 2000 and 2022 from two cosmopolitan cities and 40 remote villages of Cameroon. While 52.4% of all sequenced viruses belonged to circulating recombinant form 02_AG (CRF02_AG), the remainder were highly diverse, collectively representing seven subtypes and sub-subtypes, eight circulating recombinant forms (CRFs), and 36 highly divergent lineages that fall outside the established HIV-1M classification. Additionally, in 77 samples for which at least two genes were typed, 31% of the studied viruses apparently had fragments from viruses belonging to different clades. Furthermore, we found that the distribution of HIV-1M populations are similar between different regions of Cameroon. In contrast, HIV-1M demographics in Cameroon differ significantly from those of its neighbouring countries in the Congo basin (CB). In phylogenetic trees, viral sequences cluster according to the countries where they were sampled, suggesting that while there are minimal geographical or social barriers to viral dissemination throughout Cameroon, there is strongly impeded dispersal of HIV-1M lineages between Cameroon and other locations of the CB. This suggests that the apparent stability of highly diverse Cameroonian HIV-1M populations may be attributable to the extensive mixing of human populations within the country and the concomitant trans-national movements of major lineages with very similar degrees of fitness; coupled with the relatively infrequent inter-national transmission of these lineages from neighboring countries in the CB.
从制定治疗艾滋病毒和控制其传播的相关干预措施的角度来看,全面了解病毒的基本多样性尤为重要;尤其是在自引发全球大流行的跨物种传播事件以来病毒一直存在并不断演变的国家。在这里,我们生成了2000年至2022年间从喀麦隆的两个国际大都市和40个偏远村庄采样的HIV-1 M组(HIV-1M)分离株的gag蛋白酶(2010 bp; n=115)、部分整合酶(345 bp; n=36)和nef(719 bp; n=321)基因序列,并对这些序列进行了系统发育分析。在所有测序病毒中,52.4%属于循环重组型02_AG(CRF02_AG),而其余病毒则高度多样化,共代表了7个亚型和亚亚型、8个循环重组型(CRF)和36个高度分化的系,不属于既定的HIV-1M分类。此外,在至少对两个基因进行了分型的 77 个样本中,31% 的研究病毒明显带有属于不同支系的病毒片段。此外,我们还发现喀麦隆不同地区的 HIV-1M 群体分布相似。相比之下,喀麦隆的 HIV-1M 人口分布与刚果盆地(CB)的邻国有很大不同。在系统发生树中,病毒序列根据采样国的不同而聚类,这表明虽然在喀麦隆全境病毒传播的地理或社会障碍极小,但喀麦隆与刚果盆地其他地区之间的 HIV-1M 株系传播却受到严重阻碍。这表明,喀麦隆高度多样化的 HIV-1M 种群之所以具有明显的稳定性,可能是由于该国境内人类种群的广泛混合,以及具有非常相似适存度的主要品系随之跨国流动;再加上这些品系相对较少地从中喀边界邻国进行跨国传播。
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引用次数: 0
Cryptic transmission and novel introduction of Dengue 1 and 2 genotypes in Colombia 哥伦比亚登革热 1 号和 2 号基因型的隐性传播和新型引入
IF 5.3 2区 医学 Q1 VIROLOGY Pub Date : 2024-08-31 DOI: 10.1093/ve/veae068
David Martínez, Marcela Gómez, Carolina Hernández, Sandra Campo-Palacio, Marina González-Robayo, Marcela Montilla, Norma Pavas-Escobar, Catalina Tovar-Acero, Lillys Geovo-Arias, Esilda Valencia-Urrutia, Nayade Córdoba-Renteria, Marlen Y Carrillo-Hernandez, Julian Ruiz-Saenz, Marlen Martinez-Gutierrez, Alberto Paniz-Mondolfi, Luz H Patiño, Marina Muñoz, Juan David Ramírez
Dengue fever remains as a public health challenge in Colombia, standing as the most prevalent infectious disease in the country. The cyclic nature of dengue epidemics, occurring approximately every three years, is intricately linked to meteorological events like El Niño Southern Oscillation (ENSO). Therefore, the Colombian system faces challenges in genomic surveillance. This study aimed to evaluate local dengue virus (DENV) transmission and genetic diversity in four Colombian departments with heterogeneous incidence patterns (Department is first level territorial units in Colombia). For this study, we processed 26t6 serum samples to identify DENV. Subsequently, we obtained 118 genome sequences by sequencing DENV genomes from serum samples of 134 patients infected with DENV-1 and DENV-2 serotypes. The predominant serotype was DENV-2 (108/143), with the Asian-American (AA) genotype (91/118) being the most prevalent one. Phylogenetic analysis revealed concurrent circulation of two lineages of both DENV-2 AA and DENV-1 V, suggesting ongoing genetic exchange with sequences from Venezuela and Cuba. The continuous migration of Venezuelan citizens into Colombia can contribute to this exchange, emphasizing the need for strengthened prevention measures in border areas. Notably, the Time to Most Recent Common Ancestor analysis identified cryptic transmission of DENV-2 AA since approximately 2015, leading to the recent epidemic. This challenges the notion that major outbreaks are solely triggered by recent virus introductions, emphasizing the importance of active genomic surveillance. The study also highlighted the contrasting selection pressures on DENV-1 V and DENV-2 AA, with the latter experiencing positive selection, possibly influencing its transmissibility. The presence of a cosmopolitan genotype in Colombia, previously reported in Brazil and Peru, raises concerns about transmission routes, emphasizing the necessity for thorough DENV evolution studies. Despite limitations, the study underscores genomic epidemiology’s crucial role in early detection and comprehension of DENV genotypes, recommending the use of advanced sequencing techniques as an early warning system to help prevent and control dengue outbreaks in Colombia and worldwide.
登革热仍然是哥伦比亚的一项公共卫生挑战,是该国最流行的传染病。登革热流行的周期性(大约每三年发生一次)与厄尔尼诺南方涛动(ENSO)等气象事件密切相关。因此,哥伦比亚的基因组监测系统面临着挑战。本研究旨在评估登革热病毒(DENV)在哥伦比亚四个具有不同发病模式的省(省是哥伦比亚的一级领土单位)的传播情况和遗传多样性。在这项研究中,我们处理了 26t6 份血清样本以鉴定 DENV。随后,我们对134名感染DENV-1和DENV-2血清型的患者血清样本中的DENV基因组进行测序,获得了118个基因组序列。最主要的血清型是 DENV-2(108/143),其中亚裔美国人(AA)基因型(91/118)最为流行。系统发生学分析表明,DENV-2 AA 和 DENV-1 V 的两个系同时存在,这表明与委内瑞拉和古巴的序列正在进行遗传交流。委内瑞拉公民向哥伦比亚的持续迁移可能会促成这种交换,这强调了在边境地区加强预防措施的必要性。值得注意的是,"最近共同祖先时间 "分析发现,DENV-2 AA 的隐性传播大约始于 2015 年,导致了最近的疫情。这挑战了重大疫情仅由近期病毒引入引发的观点,强调了积极开展基因组监测的重要性。研究还强调了DENV-1 V和DENV-2 AA的选择压力对比,后者经历了正选择,可能影响了其传播性。哥伦比亚出现了一种世界性的基因型,而此前在巴西和秘鲁也有报道,这引起了人们对传播途径的担忧,强调了对 DENV 演化进行深入研究的必要性。尽管存在局限性,但这项研究强调了基因组流行病学在早期检测和理解 DENV 基因型方面的关键作用,建议使用先进的测序技术作为早期预警系统,帮助预防和控制登革热在哥伦比亚和全球的爆发。
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引用次数: 0
Intrahost evolution leading to distinct lineages in the upper and lower respiratory tracts during SARS-CoV-2 prolonged infection 在 SARS-CoV-2 长期感染过程中,宿主内进化导致上呼吸道和下呼吸道出现不同的血系
IF 5.3 2区 医学 Q1 VIROLOGY Pub Date : 2024-08-31 DOI: 10.1093/ve/veae073
Majdouline El Moussaoui, Sebastien Bontems, Cecile Meex, Marie-Pierre Hayette, Marie Lejeune, Samuel L Hong, Simon Dellicour, Michel Moutschen, Nadine Cambisano, Nathalie Renotte, Vincent Bours, Gilles Darcis, Maria Artesi, Keith Durkin
Accumulating evidence points to persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised individuals as a source of novel lineages. While intrahost evolution of the virus in chronically infected patients has previously been reported, existing knowledge is primarily based on samples from the nasopharynx. In this study, we investigate the intrahost evolution and genetic diversity that accumulated during a prolonged SARS-CoV-2 infection with the Omicron sublineage BF.7, estimated to have persisted for over one year in an immunosuppressed patient. Based on the sequencing of eight samples collected at six time points, we identified 87 intrahost single-nucleotide variants (iSNVs), two indels, and a 362 bp deletion. Our analysis revealed distinct viral genotypes in the nasopharyngeal (NP), endotracheal aspirate (ETA), and bronchoalveolar (BAL) samples. This suggests that NP samples may not offer a comprehensive representation of the overall intrahost viral diversity. Our findings not only demonstrate that the Omicron sublineage BF.7 can further diverge from its already exceptionally mutated state but also highlight that patients chronically infected with SARS-CoV-2 can develop genetically specific viral populations across distinct anatomical compartments. This provides novel insights into the intricate nature of viral diversity and evolution dynamics in persistent infections.
越来越多的证据表明,免疫力低下的人持续感染严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)是新病毒系的来源。虽然以前曾报道过慢性感染患者体内病毒的宿主内进化,但现有的知识主要是基于鼻咽部的样本。在本研究中,我们研究了一名免疫抑制患者在长期感染 SARS-CoV-2 期间积累的 Omicron 亚系 BF.7 的宿主内进化和遗传多样性。根据在六个时间点采集的八个样本的测序结果,我们发现了 87 个宿主内单核苷酸变异(iSNV)、两个嵌合体和一个 362 bp 的缺失。我们的分析表明,鼻咽部(NP)、气管内吸出物(ETA)和支气管肺泡(BAL)样本中的病毒基因型各不相同。这表明鼻咽样本可能无法全面代表宿主体内病毒的整体多样性。我们的研究结果不仅证明了 Omicron 亚系 BF.7 可以从其已经异常变异的状态进一步分化,而且还强调了慢性感染 SARS-CoV-2 的患者可以在不同的解剖结构中形成具有特定基因的病毒群。这为了解持续感染中病毒多样性和进化动态的复杂性提供了新的视角。
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引用次数: 0
Intra- and inter-subtype HIV diversity between 1994 and 2018 in southern Uganda: a longitudinal population-based study 1994 年至 2018 年乌干达南部艾滋病毒亚型内和亚型间的多样性:一项基于人口的纵向研究
IF 5.3 2区 医学 Q1 VIROLOGY Pub Date : 2024-08-23 DOI: 10.1093/ve/veae065
Seungwon Kim, Godfrey Kigozi, Michael A Martin, Ronald M Galiwango, Thomas C Quinn, Andrew D Redd, Robert Ssekubugu, David Bonsall, Deogratius Ssemwanga, Andrew Rambaut, Joshua T Herbeck, Steven J Reynolds, Brian Foley, Lucie Abeler-Dörner, Christophe Fraser, Oliver Ratmann, Joseph Kagaayi, Oliver Laeyendecker, M Kate Grabowski
There is limited data on HIV evolutionary trends in African populations. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a twenty-four-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from persons living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994 to 2018) and four hyperendemic Lake Victoria fishing communities (2011 to 2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was evaluated using the Shannon diversity index and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Demographic history of HIV was inferred using a coalescent-based Bayesian Skygrid model. Evolutionary dynamics were assessed among demographic and behavioral population sub-groups, including by migration status. 9,931 HIV sequences were available from 4,999 PLHIV, including 3,060 and 1,939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (p<0.001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (p<0.001). The proportion of viruses classified as recombinants significantly increased by nearly four-fold from 12.2% in 1995 to 44.8% in 2017. Inter-subtype HIV diversity has generally increased. While intra-subtype p24 genetic diversity and divergence leveled off after 2014, intra-subtype gp41 diversity, effective population size, and divergence increased through 2017. Intra- and inter-subtype viral diversity increased across all demographic and behavioral population sub-groups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development.
有关非洲人群中 HIV 演变趋势的数据十分有限。我们利用拉卡伊社区队列研究(Rakai Community Cohort Study)的 HIV 序列和调查数据,评估了乌干达南部地区 HIV 病毒多样性和基因分化的变化,该研究跨越了 HIV 预防和治疗项目的引入和扩大的二十四年。Gag (p24) 和 env (gp41) HIV 数据来自 31 个内陆半城市贸易和农业社区(1994 年至 2018 年)和 4 个维多利亚湖高流行性渔业社区(2011 年至 2018 年)的艾滋病毒感染者。艾滋病毒亚型是通过系统发生学确认的重组鉴定程序确定的。亚型间多样性采用香农多样性指数进行评估,亚型内多样性采用核苷酸多样性和成对 TN93 遗传距离进行评估。利用根尖距离和成对 TN93 遗传距离分析测量遗传差异。使用基于聚合的贝叶斯 Skygrid 模型推断了 HIV 的流行历史。评估了人口和行为亚群之间的进化动态,包括迁移状况。从 4999 名艾滋病毒感染者中获得了 9931 个艾滋病毒序列,其中包括分别居住在内陆和渔业社区的 3060 人和 1939 人。在内陆社区,A1亚型病毒的比例从1995年的14.3%上升到2017年的25.9%(p<0.001),而D亚型病毒的比例从1995年的73.2%下降到2017年的28.2%(p<0.001)。被归类为重组病毒的比例从 1995 年的 12.2% 大幅增至 2017 年的 44.8%,增长了近四倍。艾滋病毒亚型间的多样性普遍增加。2014 年后,亚型内 p24 遗传多样性和分化趋于平稳,而亚型内 gp41 多样性、有效种群规模和分化则在 2017 年有所增加。亚型内和亚型间病毒多样性在所有人口和行为人群亚群中都有所增加,包括近期无迁徙史或无社区外性伴侣的人群。这项研究为我们提供了有关艾滋病防治计划扩大后人群层面艾滋病病毒演变动态的见解。持续的分子监测可使人们更好地了解驱动人群艾滋病病毒进化的动态,并为疫情控制和疫苗开发提供重要启示。
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引用次数: 0
Evolution of the Cytomegalovirus RL11 Gene Family in Old World monkeys and Great Apes 巨细胞病毒 RL11 基因家族在旧世界猴子和类人猿中的进化
IF 5.3 2区 医学 Q1 VIROLOGY Pub Date : 2024-08-23 DOI: 10.1093/ve/veae066
Ulad Litvin, Eddie C.Y Wang, Richard J Stanton, Ceri A Fielding, Joseph Hughes
Cytomegalovirus is a genus of herpesviruses, members of which share a long history of co-evolution with their primate hosts including Great Apes, Old and New World monkeys. These viruses are ubiquitous within their host populations and establish lifelong infection in most individuals. Although asymptomatic in healthy individuals, infection poses a significant risk to individuals with a weakened or underdeveloped immune system. The genome of human cytomegalovirus is the largest among human-infecting viruses, and comprises at least fifteen separate gene families, which may have arisen by gene duplication. Within human cytomegalovirus, the RL11 gene family is the largest. RL11 genes are non-essential in vitro but have immune evasion roles that are likely critical to persistence in vivo. These genes demonstrate an extreme level of inter-species and intra-strain sequence diversity, that makes it challenging to deduce the evolutionary relationships within this gene family. Understanding the evolutionary relationships of these genes, especially accurate ortholog identification, is essential for reconstructing ancestral genomes, deciphering gene repertoire and order, and enabling reliable functional analyses across the Cytomegalovirus species, thereby offering insights into evolutionary processes, genetic diversity, and the functional significance of genes. In this work, we combined in silico genome screening with sequence-based and structure-guided phylogenetic analysis to reconstruct the evolutionary history of the RL11 gene family. We confirmed that RL11 genes are unique to cytomegaloviruses of Old World monkeys and Great Apes, showing that this gene family was formed by multiple early duplication events and later lineage-specific losses. We identified four main clades of RL11 genes and showed that their expansions were mainly lineage-specific and happened independently in cytomegaloviruses of Great Apes, African Old World monkeys and Asian Old World monkeys. We also identified groups of orthologous genes across the Cytomegalovirus tree showing that some human cytomegalovirus-specific RL11 genes emerged before the divergence of human and chimpanzee cytomegaloviruses but were subsequently lost in the latter. The extensive and dynamic species-specific evolution of this gene family suggests their functions target elements of host immunity that have similarly co-evolved during speciation.
巨细胞病毒是疱疹病毒的一个属,其成员与其灵长类宿主(包括类人猿、新旧世界猴子)有着共同进化的悠久历史。这些病毒在宿主群体中无处不在,并在大多数个体中形成终生感染。虽然健康人感染后无症状,但对于免疫系统较弱或发育不全的人来说,感染会带来很大风险。人类巨细胞病毒的基因组是人类感染病毒中最大的,由至少 15 个独立的基因家族组成,这些基因家族可能是通过基因复制产生的。在人类巨细胞病毒中,RL11 基因家族是最大的。RL11 基因在体外是非基本的,但具有免疫逃避的作用,可能对体内的持续存在至关重要。这些基因在物种间和菌株内表现出极高的序列多样性,这使得推断该基因家族内部的进化关系具有挑战性。了解这些基因的进化关系,特别是准确鉴定直向同源物,对于重建祖先基因组、破译基因剧目和顺序以及在巨细胞病毒物种间进行可靠的功能分析至关重要,从而为了解进化过程、遗传多样性和基因的功能意义提供见解。在这项工作中,我们结合了基于序列和结构指导的系统发育分析,对 RL11 基因家族的进化历史进行了硅学基因组筛选。我们证实了 RL11 基因是旧世界猴和类人猿巨细胞病毒所独有的,表明该基因家族是由多个早期复制事件和后来特定世系的丢失而形成的。我们发现了 RL11 基因的四个主要支系,并表明它们的扩展主要是针对特定世系的,而且在类人猿、非洲旧世界猴和亚洲旧世界猴的巨细胞病毒中是独立发生的。我们还确定了巨细胞病毒树上的同源基因组,表明一些人类巨细胞病毒特异性 RL11 基因在人类和黑猩猩巨细胞病毒分化之前就已出现,但随后在黑猩猩巨细胞病毒中消失。该基因家族广泛而动态的物种特异性进化表明,它们的功能是针对宿主免疫元素的,而宿主免疫元素在物种进化过程中也发生了类似的共同进化。
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引用次数: 0
The tissue virome of black-spotted frogs reveals a diversity of uncharacterized viruses. 黑斑蛙组织病毒组揭示了未定性病毒的多样性。
IF 5.5 2区 医学 Q1 VIROLOGY Pub Date : 2024-08-22 eCollection Date: 2024-01-01 DOI: 10.1093/ve/veae062
Chenxi Li, Yazhou Hu, Yuhang Liu, Nan Li, Le Yi, Changchun Tu, Biao He

Amphibians are an essential class in the maintenance of global ecosystem equilibrium, but they face serious extinction risks driven by climate change and infectious diseases. Unfortunately, the virus diversity harbored by these creatures has been rarely investigated. By profiling the virus flora residing in different tissues of 100 farmed black-spotted frogs (Rana nigromaculata) using a combination of DNA and RNA viromic methods, we captured 28 high-quality viral sequences covering at least 11 viral families. Most of these sequences were remarkably divergent, adding at least 10 new species and 4 new genera within the families Orthomyxoviridae, Adenoviridae, Nodaviridae, Phenuiviridae, and Picornaviridae. We recovered five orthomyxovirus segments, with three distantly neighboring two Chinese fish-related viruses. The recombination event of frog virus 3 occurred among the frog and turtle strains. The relative abundance and molecular detection revealed different tissue tropisms of these viruses, with the orthomyxovirus and adenoviruses being enteric and probably also neurotropic, but the new astrovirus and picornavirus being hepatophilic. These results expand the spectrum of viruses harbored by anurans, highlighting the necessity to continuously monitor these viruses and to investigate the virus diversity in a broader area with more diverse amphibian species.

两栖动物是维持全球生态系统平衡的重要类群,但它们面临着气候变化和传染病导致的严重灭绝风险。遗憾的是,人们很少对这些生物所携带的病毒多样性进行研究。我们采用 DNA 和 RNA 病毒组学方法,对 100 只养殖黑斑蛙(Rana nigromaculata)不同组织中的病毒群进行了分析,捕获了 28 个高质量病毒序列,涵盖至少 11 个病毒科。这些序列中的大多数都有显著的差异,在正粘病毒科、腺病毒科、Nodaviridae、Phenuiviridae 和 Picornaviridae 中至少增加了 10 个新种和 4 个新属。我们发现了5个正粘病毒片段,其中3个与2个中国鱼类相关病毒相邻。蛙病毒 3 的重组事件发生在蛙毒株和龟毒株之间。这些病毒的相对丰度和分子检测结果表明,它们具有不同的组织滋养特性,其中正粘病毒和腺病毒具有肠道滋养特性,也可能具有神经滋养特性,而新的蛙病毒和皮卡病毒则具有嗜肝特性。这些结果扩大了无尾类动物所携带病毒的范围,突出表明有必要持续监测这些病毒,并在两栖动物物种更加多样化的更广阔区域调查病毒的多样性。
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引用次数: 0
Prospects for a sequence-based taxonomy of influenza A virus subtypes. 基于序列的甲型流感病毒亚型分类法的前景。
IF 5.5 2区 医学 Q1 VIROLOGY Pub Date : 2024-08-17 eCollection Date: 2024-01-01 DOI: 10.1093/ve/veae064
Art F Y Poon

Hemagglutinin (HA) and neuraminidase (NA) proteins are the primary antigenic targets of influenza A virus (IAV) infections. IAV infections are generally classified into subtypes of HA and NA proteins, e.g. H3N2. Most of the known subtypes were originally defined by a lack of antibody cross-reactivity. However, genetic sequencing has played an increasingly important role in characterizing the evolving diversity of IAV. Novel subtypes have recently been described solely by their genetic sequences, and IAV infections are routinely subtyped by molecular assays, or the comparison of sequences to references. In this study, I carry out a comparative analysis of all available IAV protein sequences in the Genbank database (over 1.1 million, reduced to 272,292 unique sequences prior to phylogenetic reconstruction) to determine whether the serologically defined subtypes can be reproduced with sequence-based criteria. I show that a robust genetic taxonomy of HA and NA subtypes can be obtained using a simple clustering method, namely, by progressively partitioning the phylogeny on its longest internal branches. However, this taxonomy also requires some amendments to the current nomenclature. For example, two IAV isolates from bats previously characterized as a divergent lineage of H9N2 should be separated into their own subtype. With the exception of these small and highly divergent lineages, the phylogenies relating each of the other six genomic segments do not support partitions into major subtypes.

血凝素(HA)和神经氨酸酶(NA)蛋白是甲型流感病毒(IAV)感染的主要抗原目标。IAV 感染一般分为 HA 和 NA 蛋白亚型,如 H3N2。大多数已知亚型最初是通过缺乏抗体交叉反应来定义的。然而,基因测序在描述 IAV 不断演变的多样性方面发挥着越来越重要的作用。最近,一些新的亚型仅通过其基因序列就被描述出来,而 IAV 感染通常是通过分子检测或将序列与参考文献进行比较来确定亚型的。在本研究中,我对 Genbank 数据库中所有可用的 IAV 蛋白序列(超过 110 万个,在系统发育重建前已减少到 272 292 个唯一序列)进行了比较分析,以确定血清学定义的亚型是否可以通过基于序列的标准再现。我的研究表明,使用简单的聚类方法,即在最长的内部分支上逐步划分系统发育,就能获得稳健的 HA 和 NA 亚型遗传分类法。不过,这种分类法也需要对目前的命名法进行一些修改。例如,以前被定性为 H9N2 分歧系的两个蝙蝠 IAV 分离物应被分离成各自的亚型。除了这些高度分化的小系外,与其他六个基因组片段相关的系统发育并不支持将其划分为主要亚型。
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引用次数: 0
GALV-KoRV-related retroviruses in diverse Australian and African rodent species. 澳大利亚和非洲不同啮齿动物物种中的 GALV-KoRV 相关逆转录病毒。
IF 5.3 2区 医学 Q1 VIROLOGY Pub Date : 2024-08-01 DOI: 10.1093/ve/veae061
Joshua A Hayward, Shuoshuo Tian, Gilda Tachedjian
The enigmatic origins and transmission events of the gibbon ape leukemia virus (GALV) and its close relative, the koala retrovirus (KoRV) have been a source of enduring debate. Bats and rodents are each proposed as major reservoirs of interspecies transmission, with ongoing efforts to identify additional animal hosts of GALV-KoRV-related retroviruses. In this study, we identified nine rodent species as novel hosts of GALV-KoRV-related retroviruses. Included among these hosts are two African rodents, revealing the first appearance of this clade beyond the Australian and Southeast Asian region. One of these African rodents, Mastomys natalensis, carries an endogenous GALV-KoRV-related retrovirus that is fully intact and potentially still infectious. Our findings support the hypothesis that rodents are the major carriers of GALV-KoRV-related retroviruses.
长臂猿白血病病毒(GALV)及其近亲考拉逆转录病毒(KoRV)的神秘起源和传播事件一直备受争议。蝙蝠和啮齿类动物分别被认为是种间传播的主要贮源,人们还在努力确定 GALV-KoRV 相关逆转录病毒的其他动物宿主。在这项研究中,我们发现了九种啮齿类动物是 GALV-KoRV 相关逆转录病毒的新型宿主。这些宿主中包括两种非洲啮齿动物,揭示了该支系首次出现在澳大利亚和东南亚地区以外的地方。其中一种非洲啮齿类动物--Mastomys natalensis--携带的内源性 GALV-KoRV 相关逆转录病毒是完全完整的,并且仍具有潜在的传染性。我们的发现支持了啮齿类动物是 GALV-KoRV 相关逆转录病毒主要携带者的假设。
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引用次数: 0
期刊
Virus Evolution
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