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Corrigendum: Characterization of Human Herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell line 勘误:在原发性积液淋巴瘤细胞系中人类疱疹病毒8基因组整合和扩增事件的特征
Q4 VIROLOGY Pub Date : 2023-10-31 DOI: 10.3389/fviro.2023.1324885
Eva G. Álvarez, Paula Otero, Bernardo Rodríguez-Martín, Ana Pequeño-Valtierra, Iago Otero, André Vidal-Capón, Jorge Rodríguez-Castro, Juan J. Pasantes, Carmen Rivas, Jose M.C. Tubío, Daniel García-Souto
• please read through all the templates before choosing • pick the most relevant text template(s) from the following page and delete all others.• edit the text as necessary, ensuring that the original incorrect text is included for the record, please see the below. • please do not use any extra formatting when editing the templates, and only modify the red text unless absolutely necessary • submit to Frontiers following the instructions on this page.When the original text contained incorrect information, to preserve the scientific record, please include that text when editing the below templates. For example:There was a mistake in the Funding statement, an incorrect number was used. The correct number is "2015C03Bd051.". The publisher apologizes for this mistake.The original version of this article has been updated. In the published article, there was an error in the author list, and author Jose M.C. Tubío should share correspondence for this brief research report article with Daniel García-Souto. The corrected author list appears below.Eva G. Álvarez 1,2,3 † Paula Otero 1,2,3 † Bernardo Rodríguez-Martín 1 Ana Pequeño-Valtierra 1,3 Iago Otero 1,2,3 André Vidal-Capón 4 Jorge Rodríguez-Castro 1,3 Juan J. Pasantes 4 Carmen Rivas 5 Jose M.C. Tubío 1,2,3* ‡ Daniel García-Souto 1,2,3* ‡
•请在选择之前通读所有模板•从以下页面中选择最相关的文本模板并删除所有其他文本模板。•根据需要编辑文本,确保原始的错误文本包括在记录中,请参见下文。•请勿在编辑模板时使用任何额外的格式,除非绝对必要,请仅修改红色文本•按照本页的说明提交到前沿。当原始文本包含不正确的信息时,为了保存科学记录,请在编辑以下模板时包含该文本。在资金报表中有一个错误,使用了一个不正确的数字。正确的号码是“2015C03Bd051.”出版商为这个错误道歉。本文的原始版本已更新。在发表的文章中,作者列表中有一个错误,作者Jose M.C. Tubío应该与Daniel García-Souto分享这篇简短的研究报告文章的通信。更正后的作者名单如下所示。Eva G. Álvarez 1,2,3†Paula Otero 1,2,3†Bernardo Rodríguez-Martín 1 Ana Pequeño-Valtierra 1,3 Iago Otero 1,2,3 andr Vidal-Capón 4 Jorge Rodríguez-Castro 1,3 Juan J. Pasantes 4 Carmen Rivas 5 Jose M.C. Tubío 1,2,3*‡Daniel García-Souto 1,2,3*‡
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引用次数: 0
Evolution driven by a varying host environment selects for distinct HIV-1 entry phenotypes and other informative variants 由不同宿主环境驱动的进化选择了不同的HIV-1进入表型和其他信息变体
Q4 VIROLOGY Pub Date : 2023-10-30 DOI: 10.3389/fviro.2023.1291996
Shuntai Zhou, Nathan Long, Ronald Swanstrom

HIV-1 generates remarkable intra- and inter-host viral diversity during infection. In the response to the dynamic selective pressures of the host’s environment, HIV-1 evolves distinct phenotypes—biological features that provide fitness advantages. The transmitted form of HIV-1 has been shown to require a high density of CD4 on the target cell surface (as found on CD4+ T cells) and typically uses C–C chemokine receptor type 5 (CCR5) as a coreceptor during entry. This phenotype is referred to as R5T cell-tropic (or R5 T-tropic); however, HIV-1 can switch to a secondary coreceptor, C–X–C chemokine receptor type 4 (CXCR4), resulting in a X4T cell-tropic phenotype. Macrophage-tropic (or M-tropic) HIV-1 can evolve to efficiently enter cells expressing low densities of CD4 on their surface (such as macrophages/microglia). So far only CCR5-using M-tropic viruses have been found. M-tropic HIV-1 is most frequently found within the central nervous system (CNS), and infection of the CNS has been associated with neurologic impairment. It has been shown that interferon-resistant phenotypes have a selective advantage during transmission, but the underlying mechanism of this is still unclear. During untreated infection, HIV-1 evolves under selective pressure from both the humoral/antibody response and CD8+ T-cell killing. Sufficiently potent antiviral therapy can suppress viral replication, but if the antiviral drugs are not powerful enough to stop replication, then the replicating virus will evolve drug resistance. HIV-1 phenotypes are highly relevant to treatment efforts, clinical outcomes, vaccine studies, and cure strategies. Therefore, it is critical to understand the dynamics of the host environment that drive these phenotypes and how they affect HIV-1 pathogenesis. This review will provide a comprehensive discussion of HIV-1 entry and transmission, and drug-resistant phenotypes. Finally, we will assess the methods used in previous and current research to characterize these phenotypes.

HIV-1在感染过程中产生显著的宿主内和宿主间病毒多样性。在对宿主环境的动态选择压力的反应中,HIV-1进化出独特的表型-提供适应性优势的生物学特征。HIV-1的传播形式已被证明需要靶细胞表面高密度的CD4(如在CD4+ T细胞上发现的),并且通常在进入时使用C-C趋化因子受体5型(CCR5)作为辅助受体。这种表型被称为R5T细胞嗜性(或R5 t嗜性);然而,HIV-1可以转换为次级辅助受体,C-X-C趋化因子受体4型(CXCR4),导致X4T细胞表型。嗜巨噬细胞(或嗜m型)HIV-1可以进化到有效地进入表面表达低密度CD4的细胞(如巨噬细胞/小胶质细胞)。到目前为止,只发现了使用ccr5的嗜m型病毒。嗜m型HIV-1最常见于中枢神经系统(CNS),而中枢神经系统的感染与神经功能损害有关。已有研究表明,干扰素耐药表型在传播过程中具有选择性优势,但其潜在机制尚不清楚。在未经治疗的感染期间,HIV-1在体液/抗体反应和CD8+ t细胞杀伤的选择性压力下进化。足够有效的抗病毒治疗可以抑制病毒复制,但如果抗病毒药物不足以阻止复制,那么正在复制的病毒就会进化出耐药性。HIV-1表型与治疗努力、临床结果、疫苗研究和治愈策略高度相关。因此,了解驱动这些表型的宿主环境动力学以及它们如何影响HIV-1发病机制至关重要。这篇综述将提供HIV-1的进入和传播以及耐药表型的全面讨论。最后,我们将评估以前和当前研究中用于表征这些表型的方法。
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引用次数: 0
Brief research report: OM-85 reduces SARS-COV-2 viral RNA expression in nasopharyngeal cells from COVID-19 patients 研究简述:OM-85可降低COVID-19患者鼻咽细胞中SARS-COV-2病毒RNA表达
Q4 VIROLOGY Pub Date : 2023-10-26 DOI: 10.3389/fviro.2023.1111619
Gisele Cassão, Krist Helen Antunes, João Ismael Budelon Gonçalvez, Leonardo Duarte Santos, Bruno Lopes Abbadi, Cristiano Valim Bizarro, Pablo Machado, Luiz Augusto Basso, Christian Pasquali, Renato T. Stein, Ana Paula Duarte de Souza
OM-85 is a bacterial lysate from common respiratory tract pathogens, with an excellent safety profile, widely used to prevent recurrent respiratory tract infections. Several studies have been reporting the immunomodulating properties and antiviral roles of OM-85. The COVID-19 pandemic, originating in 2019, has presented a significant global public health crisis. While effective vaccines have been developed, vaccination rates vary considerably, and numerous concerning viral variants continue to emerge. The challenge persists in creating early interventions to halt the progression of the disease to its severe stages. To examine the therapeutic effect of OM-85 after SARS-CoV-2 infection and compared to recombinant human (rhINF-β) we collected nasopharyngeal cells from COVID-19 patients. The cells were treated ex-vivo with OM-85 or hrINF-β and the response was analyzed after 24h for gene expression by real-time PCR. We found that OM-85 decreased the SARS-CoV-2 N1 gene expression and increased RIG-I (DDX58) in these cells. The expression of ACE2 was undetected in these samples. These data support the antiviral effect of OM-85 against SARS-CoV-2.
OM-85是一种常见呼吸道病原体的细菌裂解物,具有良好的安全性,广泛用于预防复发性呼吸道感染。一些研究报道了OM-85的免疫调节特性和抗病毒作用。始于2019年的2019冠状病毒病大流行引发了一场重大的全球公共卫生危机。虽然已经研制出有效的疫苗,但疫苗接种率相差很大,而且许多有关的病毒变体继续出现。在制定早期干预措施以阻止疾病发展到严重阶段方面仍然存在挑战。为了检验OM-85在SARS-CoV-2感染后的治疗效果,并与重组人(rhINF-β)进行比较,我们收集了COVID-19患者的鼻咽细胞。体外分别用OM-85或hrINF-β处理细胞,24h后用real-time PCR检测基因表达情况。我们发现OM-85在这些细胞中降低了SARS-CoV-2 N1基因表达并增加了RIG-I (DDX58)。在这些样本中未检测到ACE2的表达。这些数据支持OM-85对SARS-CoV-2的抗病毒作用。
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引用次数: 0
Prediction and surveillance of de novo HCC in patients with compensated advanced chronic liver disease after hepatitis C virus eradication with direct antiviral agents 代偿性晚期慢性肝病患者丙型肝炎病毒直接抗病毒药物根除后新发HCC的预测和监测
Q4 VIROLOGY Pub Date : 2023-10-24 DOI: 10.3389/fviro.2023.1227317
Ashraf Elbahrawy, Hassan Atalla, Abdulla A. Mahmoud, Ahmed Eliwa, Alaa Alsawak, Mohamed Alboraie, Ali Madian, Ahmed Alashker, Sadek Mostafa, Ahmed Alwassief, Hussein H. Aly
The risk of hepatocellular carcinoma (HCC) diminishes in patients with hepatitis C virus (HCV)-related advanced chronic liver disease after virological cure. However, despite viral clearance, HCV-induced epigenetic alterations, immune dysregulations, and hepatic parenchymal injuries remain, contributing to de novo HCC occurrence. While HCC incidence is low (0.45 – 0.5%) in patients with advanced fibrosis (F3), the presence of liver cirrhosis and clinically significant portal hypertension increases the HCC risk. The cost-effectiveness of lifelong HCC surveillance in patients with compensated advanced chronic liver disease (cACLD) has sparked debate, raising questions about the most reliable noninvasive tests and stratification models for predicting HCC in patients with sustained virological response (SVR). Furthermore, identifying cACLD patients who may not require long-term HCC surveillance after SVR remains crucial. Several HCC risk stratification scores have been suggested for patients with cACLD, and emerging evidence supports individualized care based on personalized risk assessments. This review focuses on revising the pretreatment and posttreatment predictors of HCC, as well as the indications for HCC surveillance in cACLD patients treated with direct-acting antivirals.
丙型肝炎病毒(HCV)相关晚期慢性肝病患者病毒学治愈后发生肝细胞癌(HCC)的风险降低。然而,尽管病毒清除,hcv诱导的表观遗传改变、免疫失调和肝实质损伤仍然存在,导致HCC的新发发生。虽然晚期纤维化患者的HCC发生率较低(0.45 - 0.5%)(F3),但肝硬化和临床显著的门静脉高压症的存在增加了HCC的风险。代偿性晚期慢性肝病(cACLD)患者终身HCC监测的成本效益引发了争论,提出了关于预测持续病毒学反应(SVR)患者HCC最可靠的无创伤检测和分层模型的问题。此外,确定SVR后可能不需要长期HCC监测的cACLD患者仍然至关重要。一些HCC风险分层评分已被建议用于cACLD患者,并且新出现的证据支持基于个性化风险评估的个性化护理。本文主要综述了HCC治疗前和治疗后的预测指标,以及直接作用抗病毒药物治疗的cACLD患者HCC监测的指征。
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引用次数: 0
Clinical spectrum of COVID-19 at a national referral hospital in western Kenya during the period 2020–2021 2020-2021年期间肯尼亚西部一家国家转诊医院COVID-19的临床谱
Q4 VIROLOGY Pub Date : 2023-10-12 DOI: 10.3389/fviro.2023.1202742
Edith A. Ogalo, Edwin Gudu, Thomas Andale, Daisy Korir, Samson Ndege, Tabu Simiyu, Richard Olekuyo, Henry Mwangi, Sylvester Kimaiyo, Wilson Aruasa
Introduction We describe the clinical spectrum of COVID-19 cases in western Kenya from 6 April 2020 to 31 May 2021, providing baseline data for further studies into COVID-19 in Kenya. Methods We did a retrospective chart review of laboratory and inpatient files of patients diagnosed and managed for COVID-19 at the Moi Teaching and Referral Hospital in Kenya and analyzed the data using Stata ® version 16 (StataCorp LP, College Station, TX, USA) and calculated measures of association at 95% CI. Results The patients ( n = 1,770) had a mean age of 43 years (SD 20 years) and 55.4% were male. Close to 70% had asymptomatic disease, with the symptomatic cases largely being respiratory in nature. One-quarter had comorbidities. The case fatality rate was 13.6% ( n = 240). Male sex increased the odds of mortality by 1.69 (95% CI 1.27–2.25; p ≤ 0.001), and the presence of comorbidities increased the odds of mortality by 3.16 (95% CI 2.38–4.18; p ≤ 0.001). Those aged 59 years and above were 18 times more likely to die from COVID-19 than those below 15 years of age (95% CI 1.61–90.66; p = 0.015). Conclusion COVID-19 had a significantly high mortality rate in western Kenya. Male sex and the presence of comorbidities increased the risk of severe disease and mortality.
我们描述了2020年4月6日至2021年5月31日肯尼亚西部COVID-19病例的临床谱,为肯尼亚进一步研究COVID-19提供基线数据。方法我们对肯尼亚Moi教学和转诊医院诊断和治疗的COVID-19患者的实验室和住院档案进行回顾性图表回顾,并使用Stata®version 16 (StataCorp LP, College Station, TX, USA)分析数据,并计算95% CI的关联度量。结果1770例患者平均年龄43岁(SD 20岁),男性55.4%。近70%无症状,有症状的病例以呼吸道为主。四分之一有合并症。病死率为13.6% (n = 240)。男性使死亡率增加1.69 (95% CI 1.27-2.25;p≤0.001),合并症的存在使死亡率增加3.16 (95% CI 2.38-4.18;P≤0.001)。59岁及以上人群死于COVID-19的可能性是15岁以下人群的18倍(95% CI 1.61-90.66;P = 0.015)。结论新型冠状病毒病死率在肯尼亚西部地区较高。男性和合并症的存在增加了严重疾病和死亡的风险。
{"title":"Clinical spectrum of COVID-19 at a national referral hospital in western Kenya during the period 2020–2021","authors":"Edith A. Ogalo, Edwin Gudu, Thomas Andale, Daisy Korir, Samson Ndege, Tabu Simiyu, Richard Olekuyo, Henry Mwangi, Sylvester Kimaiyo, Wilson Aruasa","doi":"10.3389/fviro.2023.1202742","DOIUrl":"https://doi.org/10.3389/fviro.2023.1202742","url":null,"abstract":"Introduction We describe the clinical spectrum of COVID-19 cases in western Kenya from 6 April 2020 to 31 May 2021, providing baseline data for further studies into COVID-19 in Kenya. Methods We did a retrospective chart review of laboratory and inpatient files of patients diagnosed and managed for COVID-19 at the Moi Teaching and Referral Hospital in Kenya and analyzed the data using Stata ® version 16 (StataCorp LP, College Station, TX, USA) and calculated measures of association at 95% CI. Results The patients ( n = 1,770) had a mean age of 43 years (SD 20 years) and 55.4% were male. Close to 70% had asymptomatic disease, with the symptomatic cases largely being respiratory in nature. One-quarter had comorbidities. The case fatality rate was 13.6% ( n = 240). Male sex increased the odds of mortality by 1.69 (95% CI 1.27–2.25; p ≤ 0.001), and the presence of comorbidities increased the odds of mortality by 3.16 (95% CI 2.38–4.18; p ≤ 0.001). Those aged 59 years and above were 18 times more likely to die from COVID-19 than those below 15 years of age (95% CI 1.61–90.66; p = 0.015). Conclusion COVID-19 had a significantly high mortality rate in western Kenya. Male sex and the presence of comorbidities increased the risk of severe disease and mortality.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135968675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pepper mild mottle virus: a formidable foe of capsicum production—a review 辣椒轻度斑驳病毒:辣椒生产的强大敌人——综述
Q4 VIROLOGY Pub Date : 2023-10-12 DOI: 10.3389/fviro.2023.1208853
Nidhi Kumari, Vivek Sharma, Priyankaben Patel, P. N. Sharma
Viruses are one of the major restraining factors in pepper cultivation globally. Among different viruses, pepper mild mottle virus (PMMoV) is one of the most detrimental plant viruses infecting Capsicum spp. belonging to the genus Tobamovirus and Virgaviridae family. It has a monopartite positive-sense single-stranded RNA genome of 6.35 kb size. On an average, PMMoV results in 15%–40% losses in capsicum fruit yield. However, the incidence of PMMoV can reach as high as 95%, leading to substantial yield losses ranging from 75% to 95%. The virus is transmitted via contact, soil, and seeds rather than via insect vectors. PMMoV, because of its seed-borne nature, now occurs worldwide. PMMoV mainly infects Capsicum spp. under natural conditions; however, it can experimentally be transmitted to other plants species belonging to the families Solanaceae, Cucurbitaceae, Labiatae, Chenopodiaceae, and Plantaginaceae. The resistance to tobamoviruses in capsicum is conferred by L locus. Mutations in the coat protein of PMMoV are responsible for the emergence of L -mediated resistance-breaking pathotypes. The highly contagious nature of the virus, seed transmission behavior, and the emergence of virulence complicate its management through a single approach. Therefore, efforts are directed towards providing a more practical and efficient integrated management solution using the RNA interference approach; exploitation of the L gene for resistance breeding; and the inhibitory potential of natural products, systemic resistance-inducing antagonistic bacteria, and chemically synthesized silver nanoparticles. Markers linked to L alleles have been observed to accelerate capsicum breeding programs through marker-assisted selection. In this study, an attempt has been made to compile the recent developments in PMMoV biology, pathogenic variability, genomic organization, and management strategies.
病毒是全球辣椒栽培的主要制约因素之一。辣椒温和斑驳病毒(椒mild mottle virus, PMMoV)是侵染辣椒属巴氏病毒属(toamovirus)和维加病毒科(Virgaviridae)的一种危害最大的植物病毒。它有一个6.35 kb大小的单链正义RNA基因组。PMMoV导致辣椒产量平均损失15%-40%。然而,PMMoV的发生率可高达95%,导致产量损失高达75% ~ 95%。该病毒通过接触、土壤和种子传播,而不是通过昆虫媒介传播。由于其种子传播的性质,PMMoV现在在世界范围内发生。PMMoV主要在自然条件下侵染辣椒;然而,它可以通过实验传播到其他植物物种,包括茄科、葫芦科、唇形科、藜科和车前草科。辣椒对烟草病毒的抗性是由L基因座赋予的。PMMoV外壳蛋白的突变导致了L介导的抗性破坏病理型的出现。该病毒的高度传染性、种子传播行为和毒性的出现使单一方法的管理复杂化。因此,努力的方向是使用RNA干扰方法提供更实用和有效的综合管理解决方案;利用L基因进行抗性育种;以及天然产物、系统性耐药诱导拮抗细菌和化学合成纳米银的抑制潜力。与L等位基因相关的标记已被观察到通过标记辅助选择加速辣椒育种计划。在这项研究中,试图汇编PMMoV生物学,致病变异性,基因组组织和管理策略的最新进展。
{"title":"Pepper mild mottle virus: a formidable foe of capsicum production—a review","authors":"Nidhi Kumari, Vivek Sharma, Priyankaben Patel, P. N. Sharma","doi":"10.3389/fviro.2023.1208853","DOIUrl":"https://doi.org/10.3389/fviro.2023.1208853","url":null,"abstract":"Viruses are one of the major restraining factors in pepper cultivation globally. Among different viruses, pepper mild mottle virus (PMMoV) is one of the most detrimental plant viruses infecting Capsicum spp. belonging to the genus Tobamovirus and Virgaviridae family. It has a monopartite positive-sense single-stranded RNA genome of 6.35 kb size. On an average, PMMoV results in 15%–40% losses in capsicum fruit yield. However, the incidence of PMMoV can reach as high as 95%, leading to substantial yield losses ranging from 75% to 95%. The virus is transmitted via contact, soil, and seeds rather than via insect vectors. PMMoV, because of its seed-borne nature, now occurs worldwide. PMMoV mainly infects Capsicum spp. under natural conditions; however, it can experimentally be transmitted to other plants species belonging to the families Solanaceae, Cucurbitaceae, Labiatae, Chenopodiaceae, and Plantaginaceae. The resistance to tobamoviruses in capsicum is conferred by L locus. Mutations in the coat protein of PMMoV are responsible for the emergence of L -mediated resistance-breaking pathotypes. The highly contagious nature of the virus, seed transmission behavior, and the emergence of virulence complicate its management through a single approach. Therefore, efforts are directed towards providing a more practical and efficient integrated management solution using the RNA interference approach; exploitation of the L gene for resistance breeding; and the inhibitory potential of natural products, systemic resistance-inducing antagonistic bacteria, and chemically synthesized silver nanoparticles. Markers linked to L alleles have been observed to accelerate capsicum breeding programs through marker-assisted selection. In this study, an attempt has been made to compile the recent developments in PMMoV biology, pathogenic variability, genomic organization, and management strategies.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"128 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135968661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of Human Herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell line 原发性积液性淋巴瘤细胞系中人类疱疹病毒8基因组整合和扩增事件的特征
Q4 VIROLOGY Pub Date : 2023-10-02 DOI: 10.3389/fviro.2023.1253416
Eva G. Álvarez, Paula Otero, Bernardo Rodríguez-Martín, Ana Pequeño-Valtierra, Iago Otero, André Vidal-Capón, Jorge Rodríguez-Castro, Juan J. Pasantes, Carmen Rivas, Jose M.C. Tubío, Daniel García-Souto
In this study, we investigated the integration of Human Herpesvirus 8 (HHV-8) into the human genome using the primary effusion lymphoma (PEL) cell line BC-3. Through next-generation sequencing (NGS) data from multiple independent sequencing runs, we identified two highly supported HHV-8 integrants. These integrants encompassed a region of human chromosome 12 that was amplified approximately 16-fold between the junctions. Significantly, these events could represent the first known instance of HHV-8 integration into a hybrid human-viral extrachromosomal chimeric circular DNA (eccDNA). The amplified fragment contained partial or complete copies of various human genes, including SELPLG and CORO1C. Analysis of long-read Nanopore data indicated that the CpGs at the SELPLG promoter were mostly unmethylated, suggesting that the additional copies of SELPLG within this eccDNA are likely transcriptionally active. Our findings suggest that viral insertion and eccDNA amplification could be crucial mechanisms in the development of HHV-8-related cancers. In conclusion, our study provides valuable insights into the molecular mechanisms involved in HHV-8-induced oncogenesis and emphasizes the importance of investigating viral integration and eccDNAs in cancer development. Furthermore, we highlight the necessity of employing multiple independent sequencing approaches to validate integration events and avoid false positives derived from library construction artifacts.
在这项研究中,我们利用原发性积液淋巴瘤(PEL)细胞系BC-3研究了人类疱疹病毒8 (HHV-8)在人类基因组中的整合。通过来自多个独立测序运行的下一代测序(NGS)数据,我们确定了两个高度支持的HHV-8整合子。这些整合物包含了人类12号染色体的一个区域,该区域在连接之间被放大了大约16倍。值得注意的是,这些事件可能代表了HHV-8整合到杂交人类-病毒染色体外嵌合环状DNA (eccDNA)的第一个已知实例。扩增的片段含有多种人类基因的部分或完整拷贝,包括SELPLG和CORO1C。对长读纳米孔数据的分析表明,SELPLG启动子上的CpGs大部分未甲基化,这表明该eccDNA中SELPLG的额外拷贝可能具有转录活性。我们的研究结果表明,病毒插入和eccDNA扩增可能是hhv -8相关癌症发展的关键机制。总之,我们的研究为hhv -8诱导肿瘤发生的分子机制提供了有价值的见解,并强调了研究病毒整合和eccdna在癌症发展中的重要性。此外,我们强调了采用多个独立测序方法来验证集成事件的必要性,并避免了由于库构建工件而产生的误报。
{"title":"Characterization of Human Herpesvirus 8 genomic integration and amplification events in a primary effusion lymphoma cell line","authors":"Eva G. Álvarez, Paula Otero, Bernardo Rodríguez-Martín, Ana Pequeño-Valtierra, Iago Otero, André Vidal-Capón, Jorge Rodríguez-Castro, Juan J. Pasantes, Carmen Rivas, Jose M.C. Tubío, Daniel García-Souto","doi":"10.3389/fviro.2023.1253416","DOIUrl":"https://doi.org/10.3389/fviro.2023.1253416","url":null,"abstract":"In this study, we investigated the integration of Human Herpesvirus 8 (HHV-8) into the human genome using the primary effusion lymphoma (PEL) cell line BC-3. Through next-generation sequencing (NGS) data from multiple independent sequencing runs, we identified two highly supported HHV-8 integrants. These integrants encompassed a region of human chromosome 12 that was amplified approximately 16-fold between the junctions. Significantly, these events could represent the first known instance of HHV-8 integration into a hybrid human-viral extrachromosomal chimeric circular DNA (eccDNA). The amplified fragment contained partial or complete copies of various human genes, including SELPLG and CORO1C. Analysis of long-read Nanopore data indicated that the CpGs at the SELPLG promoter were mostly unmethylated, suggesting that the additional copies of SELPLG within this eccDNA are likely transcriptionally active. Our findings suggest that viral insertion and eccDNA amplification could be crucial mechanisms in the development of HHV-8-related cancers. In conclusion, our study provides valuable insights into the molecular mechanisms involved in HHV-8-induced oncogenesis and emphasizes the importance of investigating viral integration and eccDNAs in cancer development. Furthermore, we highlight the necessity of employing multiple independent sequencing approaches to validate integration events and avoid false positives derived from library construction artifacts.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"240 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135895518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biological and molecular interactions between bell pepper endornavirus and two tobamoviruses 甜椒内啡肽病毒与两种乙型病毒的生物学和分子相互作用
Q4 VIROLOGY Pub Date : 2023-09-29 DOI: 10.3389/fviro.2023.1267692
Cesar Escalante, Surasak Khankhum, Rodrigo A. Valverde
Peppers ( Capsicum spp.) are native plants to the Americas. They are cultivated worldwide for direct human consumption and industrial purposes. Peppers can be infected by acute plant viruses, which cause a variety of diseases and crop losses. However, many Capsicum species can also be infected by persistent viruses. These are emerging viruses and they do not cause apparent disease and are transmitted only vertically. Using two near-isogenic lines of bell pepper cv. Marengo, biological and molecular interactions between the persistent virus bell pepper endornavirus (BPEV) and two acute viruses, pepper mild mottle virus (PMMoV) and tobacco mild green mosaic virus (TMGMV), were evaluated by symptom expression, enzyme-linked immunosorbent assay, and RT-qPCR. The relative titer of BPEV decreased at least two-fold at 14 days after infection when BPEV-infected plants were single infected with TMGMV or in mixed infection of PMMoV and TMGMV. The presence of BPEV was associated with symptom reduction in pepper plants infected with single and mixed infections of PMMoV and TMGMV. This suggests that the ubiquitous infection of BPEV may trigger the plant immune response, and therefore, BPEV is active when the plant is infected with PMMoV and/or TMGMV.
辣椒(辣椒科)是美洲的本土植物。它们在世界范围内被种植用于人类直接消费和工业用途。辣椒可被急性植物病毒感染,引起各种疾病和作物损失。然而,许多辣椒品种也可以被持久性病毒感染。这些都是新出现的病毒,它们不会引起明显的疾病,只会垂直传播。利用甜椒cv的两个近等基因系。采用症状表达法、酶联免疫吸附法和RT-qPCR技术,研究了甜椒内啡肽病毒(BPEV)与辣椒轻度斑驳病毒(PMMoV)和烟草轻度绿花叶病毒(TMGMV)的生物学和分子相互作用。感染BPEV的植株单独感染TMGMV或PMMoV和TMGMV混合感染时,感染后14天BPEV的相对滴度至少下降2倍。BPEV的存在与PMMoV和TMGMV单一感染和混合感染辣椒植株的症状减轻有关。这表明,BPEV的普遍感染可能引发植物的免疫反应,因此,当植物感染PMMoV和/或TMGMV时,BPEV是活跃的。
{"title":"Biological and molecular interactions between bell pepper endornavirus and two tobamoviruses","authors":"Cesar Escalante, Surasak Khankhum, Rodrigo A. Valverde","doi":"10.3389/fviro.2023.1267692","DOIUrl":"https://doi.org/10.3389/fviro.2023.1267692","url":null,"abstract":"Peppers ( Capsicum spp.) are native plants to the Americas. They are cultivated worldwide for direct human consumption and industrial purposes. Peppers can be infected by acute plant viruses, which cause a variety of diseases and crop losses. However, many Capsicum species can also be infected by persistent viruses. These are emerging viruses and they do not cause apparent disease and are transmitted only vertically. Using two near-isogenic lines of bell pepper cv. Marengo, biological and molecular interactions between the persistent virus bell pepper endornavirus (BPEV) and two acute viruses, pepper mild mottle virus (PMMoV) and tobacco mild green mosaic virus (TMGMV), were evaluated by symptom expression, enzyme-linked immunosorbent assay, and RT-qPCR. The relative titer of BPEV decreased at least two-fold at 14 days after infection when BPEV-infected plants were single infected with TMGMV or in mixed infection of PMMoV and TMGMV. The presence of BPEV was associated with symptom reduction in pepper plants infected with single and mixed infections of PMMoV and TMGMV. This suggests that the ubiquitous infection of BPEV may trigger the plant immune response, and therefore, BPEV is active when the plant is infected with PMMoV and/or TMGMV.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"95 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135245981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hepatitis B virus infection in patients presenting for immunosuppressive cancer therapy with and without underlying HIV infection 乙型肝炎病毒感染的患者呈现免疫抑制癌症治疗伴有和不伴有潜在的HIV感染
Q4 VIROLOGY Pub Date : 2023-09-26 DOI: 10.3389/fviro.2023.1160078
Malowane H. Ngoato, Edina Amponsah-Dacosta, Ntombifuthi Blose, Selokela G. Selabe, Thembeni L. Msibi, Mojakgomo H. Motswaledi, Andrew M. Musyoki
Introduction Reactivation of hepatitis B virus (HBV) infection induced by immunosuppressive cancer therapy is associated with fulminant liver disease and death. While national guidelines recommend HBV screening and antiviral prophylaxis for patients with cancer prior to initiating immunosuppressive therapy, compliance with these measures is unclear. This study characterized the burden of HBV infection among patients diagnosed with gynecological or dermatological cancers, with or without underlying HIV infection, before initiating immunosuppressive therapy. Methods Between 2016 – 2018, we recruited study patients from the Dr George Mukhari Academic Hospital in Tshwane, South Africa. Demographic (age, sex) and clinical data (HIV test results, HIV antiviral regimen, type of cancer) were recorded using a standardized data collection form. All participants were tested for HBV surface antigen (HBsAg), and antibodies to the surface (anti-HBs) and core antigens (anti-HBc). For detection of HBV DNA, a nested polymerase chain reaction was used to amplify polymerase gene fragments which were Sanger-sequenced and analyzed using bioinformatics software. All statistical analyses were performed using R version 4.1.0 (2021-05-18) and R studio version 2022.07.2. Results Study participants were predominantly female (96.3%, 103/107) with a median (IQR) age of 50 (17.5) years. Cervical cancer was the most frequent cancer diagnosis (72%). Over half (52.3%; 56/107) of the participants were HIV positive and all but four (92.9%) on highly active antiretroviral therapy at the time of enrollment. The prevalence of chronic hepatitis B in the study population was 11.2% [95% CI:6.2-19.1], increasing to 14.3% [95% CI:6.8-26.8] in the HIV positive sub-population. The overall prevalence of occult HBV infection was 20% [95% CI:12.8-29.7], 57.9% [95% CI:33.97-78.9] of whom tested negative for all serological markers. Phylogenetic inference showed that all polymerase gene sequences generated in this study were sub-genotype A2. Mutational analysis did not reveal any drug resistance-associated amino acid variations in this study. Conclusion These findings suggest that chronic and occult HBV infections are more prevalent among cancer patients with or without underlying HIV infection compared to what has previously been reported for the general South African population. This underscores the need to scale-up universal HBV serological and molecular screening with timely institution of prophylaxis prior to initiating immunosuppressive cancer therapy.
免疫抑制癌症治疗诱导乙型肝炎病毒(HBV)感染的再激活与暴发性肝病和死亡有关。虽然国家指南建议在开始免疫抑制治疗之前对癌症患者进行HBV筛查和抗病毒预防,但这些措施的依从性尚不清楚。本研究描述了在开始免疫抑制治疗之前,诊断为妇科或皮肤病癌症的患者,无论是否有潜在的HIV感染,HBV感染的负担。方法2016 - 2018年间,我们从南非茨瓦内的Dr George Mukhari学术医院招募了研究患者。使用标准化数据收集表记录人口统计(年龄、性别)和临床数据(艾滋病毒检测结果、艾滋病毒抗病毒方案、癌症类型)。所有参与者均检测HBV表面抗原(HBsAg)、表面抗体(anti-HBs)和核心抗原(anti-HBc)。检测HBV DNA时,采用巢式聚合酶链反应扩增聚合酶基因片段,进行sanger测序,并用生物信息学软件进行分析。所有统计分析均使用R 4.1.0版本(2021-05-18)和R studio版本2022.07.2进行。结果研究参与者以女性为主(96.3%,103/107),中位(IQR)年龄为50(17.5)岁。宫颈癌是最常见的癌症诊断(72%)。过半(52.3%;56/107)的参与者是HIV阳性的,除了4人(92.9%)外,所有参与者在入组时都在接受高效抗逆转录病毒治疗。慢性乙型肝炎在研究人群中的患病率为11.2% [95% CI:6.2-19.1],在HIV阳性亚人群中增加到14.3% [95% CI:6.8-26.8]。隐匿性HBV感染的总体患病率为20% [95% CI:12.8-29.7], 57.9% [95% CI:33.97-78.9],其中所有血清学标志物检测均为阴性。系统发育推断本研究产生的聚合酶基因序列均为A2亚基因型。突变分析在本研究中未发现任何与耐药相关的氨基酸变异。这些发现表明,与之前报道的南非普通人群相比,慢性和隐匿性HBV感染在伴有或未伴有潜在HIV感染的癌症患者中更为普遍。这强调了在开始免疫抑制癌症治疗之前,需要扩大普遍的HBV血清学和分子筛查,及时建立预防制度。
{"title":"Hepatitis B virus infection in patients presenting for immunosuppressive cancer therapy with and without underlying HIV infection","authors":"Malowane H. Ngoato, Edina Amponsah-Dacosta, Ntombifuthi Blose, Selokela G. Selabe, Thembeni L. Msibi, Mojakgomo H. Motswaledi, Andrew M. Musyoki","doi":"10.3389/fviro.2023.1160078","DOIUrl":"https://doi.org/10.3389/fviro.2023.1160078","url":null,"abstract":"Introduction Reactivation of hepatitis B virus (HBV) infection induced by immunosuppressive cancer therapy is associated with fulminant liver disease and death. While national guidelines recommend HBV screening and antiviral prophylaxis for patients with cancer prior to initiating immunosuppressive therapy, compliance with these measures is unclear. This study characterized the burden of HBV infection among patients diagnosed with gynecological or dermatological cancers, with or without underlying HIV infection, before initiating immunosuppressive therapy. Methods Between 2016 – 2018, we recruited study patients from the Dr George Mukhari Academic Hospital in Tshwane, South Africa. Demographic (age, sex) and clinical data (HIV test results, HIV antiviral regimen, type of cancer) were recorded using a standardized data collection form. All participants were tested for HBV surface antigen (HBsAg), and antibodies to the surface (anti-HBs) and core antigens (anti-HBc). For detection of HBV DNA, a nested polymerase chain reaction was used to amplify polymerase gene fragments which were Sanger-sequenced and analyzed using bioinformatics software. All statistical analyses were performed using R version 4.1.0 (2021-05-18) and R studio version 2022.07.2. Results Study participants were predominantly female (96.3%, 103/107) with a median (IQR) age of 50 (17.5) years. Cervical cancer was the most frequent cancer diagnosis (72%). Over half (52.3%; 56/107) of the participants were HIV positive and all but four (92.9%) on highly active antiretroviral therapy at the time of enrollment. The prevalence of chronic hepatitis B in the study population was 11.2% [95% CI:6.2-19.1], increasing to 14.3% [95% CI:6.8-26.8] in the HIV positive sub-population. The overall prevalence of occult HBV infection was 20% [95% CI:12.8-29.7], 57.9% [95% CI:33.97-78.9] of whom tested negative for all serological markers. Phylogenetic inference showed that all polymerase gene sequences generated in this study were sub-genotype A2. Mutational analysis did not reveal any drug resistance-associated amino acid variations in this study. Conclusion These findings suggest that chronic and occult HBV infections are more prevalent among cancer patients with or without underlying HIV infection compared to what has previously been reported for the general South African population. This underscores the need to scale-up universal HBV serological and molecular screening with timely institution of prophylaxis prior to initiating immunosuppressive cancer therapy.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"63 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135719306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dolutegravir resistance in sub-Saharan Africa: should resource-limited settings be concerned for future treatment? 撒哈拉以南非洲地区的杜鲁特韦耐药性:未来的治疗是否应关注资源有限的地区?
Q4 VIROLOGY Pub Date : 2023-09-25 DOI: 10.3389/fviro.2023.1253661
Doreen Kamori, Godfrey Barabona
In sub-Saharan Africa (SSA) the burden of non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV drug resistance (HIVDR) has been high over the years. Therefore, in 2018 the World Health Organization (WHO) recommended a regimen based on a integrase strand transfer inhibitor (INSTI), dolutegravir, as the default first-line antiretroviral therapy (ART) in countries in SSA. The scale-up of DTG-based regimens in SSA has gained significant momentum since 2018 and has continued to expand across multiple countries in recent years. However, whether or not the DTG robustness experienced in the developed world will also be achieved in SSA settings is still an important question. Evidence generated from in vitro and in vivo studies suggests that the emergence of DTG HIVDR is HIV-1 subtype dependent. These findings demonstrate that the extensive HIV-1 diversity in SSA can influence DTG effectiveness and the emergence of drug resistance. In addition, the programmatic approach to the transition to DTG adopted by many countries in the SSA region potentially exposes individuals to DTG functional monotherapy, which is associated with the emergence of DTG resistance. In this mini review, we describe the current trends of the effectiveness of DTG as reflected by viral suppression and DTG resistance. Furthermore, we explore how HIV-1 diversity and the programmatic approach in SSA could shape DTG effectiveness and DTG HIVDR in the region.
在撒哈拉以南非洲(SSA),非核苷逆转录酶抑制剂(NNRTI)艾滋病毒耐药性(HIVDR)的负担多年来一直很高。因此,2018年,世界卫生组织(WHO)推荐了一种基于整合酶链转移抑制剂(INSTI)的方案,多替格拉韦(dolutegravir)作为SSA国家默认的一线抗逆转录病毒疗法(ART)。自2018年以来,在撒哈拉以南非洲扩大以双胍为基础的治疗方案的势头显著,近年来在多个国家继续扩大。然而,发达国家所经历的DTG稳健性是否也能在SSA环境中实现,仍然是一个重要的问题。来自体外和体内研究的证据表明,DTG HIVDR的出现依赖于HIV-1亚型。这些发现表明,SSA中广泛的HIV-1多样性可以影响DTG的有效性和耐药性的出现。此外,SSA地区许多国家采用的向DTG过渡的规划方法可能使个体暴露于DTG功能单一疗法,这与DTG耐药的出现有关。在这篇简短的综述中,我们描述了DTG有效性的当前趋势,包括病毒抑制和DTG耐药性。此外,我们探讨了SSA的HIV-1多样性和规划方法如何影响该地区DTG的有效性和DTG的hiv - dr。
{"title":"Dolutegravir resistance in sub-Saharan Africa: should resource-limited settings be concerned for future treatment?","authors":"Doreen Kamori, Godfrey Barabona","doi":"10.3389/fviro.2023.1253661","DOIUrl":"https://doi.org/10.3389/fviro.2023.1253661","url":null,"abstract":"In sub-Saharan Africa (SSA) the burden of non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV drug resistance (HIVDR) has been high over the years. Therefore, in 2018 the World Health Organization (WHO) recommended a regimen based on a integrase strand transfer inhibitor (INSTI), dolutegravir, as the default first-line antiretroviral therapy (ART) in countries in SSA. The scale-up of DTG-based regimens in SSA has gained significant momentum since 2018 and has continued to expand across multiple countries in recent years. However, whether or not the DTG robustness experienced in the developed world will also be achieved in SSA settings is still an important question. Evidence generated from in vitro and in vivo studies suggests that the emergence of DTG HIVDR is HIV-1 subtype dependent. These findings demonstrate that the extensive HIV-1 diversity in SSA can influence DTG effectiveness and the emergence of drug resistance. In addition, the programmatic approach to the transition to DTG adopted by many countries in the SSA region potentially exposes individuals to DTG functional monotherapy, which is associated with the emergence of DTG resistance. In this mini review, we describe the current trends of the effectiveness of DTG as reflected by viral suppression and DTG resistance. Furthermore, we explore how HIV-1 diversity and the programmatic approach in SSA could shape DTG effectiveness and DTG HIVDR in the region.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135864646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Frontiers in virology
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