Virus research最新文献_第6页

Signature of viral fossils: a comparative genomics approach to understand the diversity of endogenous retroviruses in bats 病毒化石的特征：了解蝙蝠内源性逆转录病毒多样性的比较基因组学方法。

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2024-10-25 DOI: 10.1016/j.virusres.2024.199484

Vinita Lamba , Ipsita Herlekar , Durbadal Chatterjee , Kirnalee Patel , Kritika M. Garg , Balaji Chattopadhyay

Endogenous retroviruses (ERVs) are traces of past viral infections commonly found in vertebrate genomes. Many ERVs are tightly regulated by the host genomes and co-opted for various functions within the hosts. Bats are the only true volant mammals, with the smallest mammalian genomes and a high fraction of ERVs within the genomes. They are important hosts for various zoonotic viral pathogens and can effectively modulate their immune response to tolerate viral infections. Integrations of retroviruses have been implicated as one of the mechanisms by which bats have co-evolved strategies to combat viral infections. In this study, we investigated the diversity of ERVs in over 40 publicly available bat genomes to understand the distribution and the evolution of ERVs within bats. We observed all classes of ERVs within bat genomes including even the complex lenti retroviruses. Alpha and spuma retroviruses which are generally considered rare in mammals, were common within bats. We observed a positive correlation between bat genome size and length of ERV elements. Interestingly, nearly 30 % of the ERVs within bats are intact suggesting a recent origin or co-option by the host genome. Future studies focusing on comparative genomic and experimental data will be critical to understand the role of these ERVs in host genome evolution.

内源性逆转录病毒（ERV）是脊椎动物基因组中常见的过去病毒感染的痕迹。许多 ERV 受到宿主基因组的严格调控，并在宿主体内发挥各种功能。蝙蝠是唯一真正的易变哺乳动物，拥有哺乳动物中最小的基因组，基因组中ERV的比例很高。它们是各种人畜共患病毒病原体的重要宿主，能有效调节自身的免疫反应，耐受病毒感染。逆转录病毒的整合被认为是蝙蝠共同进化对抗病毒感染策略的机制之一。在这项研究中，我们调查了40多个公开蝙蝠基因组中ERV的多样性，以了解ERV在蝙蝠体内的分布和进化。我们在蝙蝠基因组中观察到了所有类别的ERV，甚至包括复杂的lenti逆转录病毒。通常被认为在哺乳动物中罕见的α和spuma逆转录病毒在蝙蝠中很常见。我们观察到，蝙蝠基因组的大小与ERV元件的长度呈正相关。有趣的是，蝙蝠体内近30%的ERV都是完整的，这表明ERV是最近才起源的，或者是被宿主基因组共用的。未来的研究将侧重于比较基因组和实验数据，这对了解这些ERV在宿主基因组进化中的作用至关重要。

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引用次数: 0

Advances in human norovirus research: Vaccines, genotype distribution and antiviral strategies 人类诺如病毒研究进展：疫苗、基因型分布和抗病毒策略。

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2024-10-23 DOI: 10.1016/j.virusres.2024.199486

JunLi Chen , ZhengChao Cheng , Jing Chen , Lingling Qian , Haoran Wang , YuWei Liu

Norovirus, belonging to the Caliciviridae family, is a non-enveloped, positive-sense single-stranded RNA virus. It is widely acknowledged as a significant etiological agent responsible for non-bacterial acute gastroenteritis and considered a major cause thereof. Norovirus is primarily tranmitted via fecal-oral route, but can also be transmitted via airborne routes. Clinical manifestations often include symptoms associated with acute gastroenteritis, like nausea, vomiting, watery diarrhea, stomach cramps, and others. Due to the specific pathogenic mechanism of the virus, and genomic diversity, there are currently no preventive vaccines or effective antiviral drugs available for treating norovirus-induced acute gastroenteritis infections. The management of such infections mainly relies on oral rehydration therapy while prevention necessitates adherence to personal hygiene measures.

The present paper discusses the nature, transmission route, clinical manifestations, immune response mechanism, and vaccine research of Norovirus. The objective of this review manuscript is to systematically gather, analyze, and summarize recent research and investigations on norovirus in order to enhance our understanding of its characteristics and pathogenesis. This not only facilitates subsequent researchers in acquiring a more expedited and comprehensive grasp of the existing knowledge about norovirus but also provides clearer directions and goals for future studies.

诺如病毒属于卡里科病毒属，是一种无包膜的正义单链 RNA 病毒。人们普遍认为它是导致非细菌性急性肠胃炎的重要病原体，并认为它是导致非细菌性急性肠胃炎的主要原因。诺如病毒主要通过粪-口途径传播，但也可通过空气传播。临床表现通常包括与急性肠胃炎相关的症状，如恶心、呕吐、水样腹泻、胃痉挛等。由于诺如病毒具有特殊的致病机制和基因组多样性，目前还没有预防性疫苗或有效的抗病毒药物可用于治疗诺如病毒引起的急性肠胃炎感染。治疗这类感染主要依靠口服补液疗法，而预防则需要坚持个人卫生措施。本文讨论了诺如病毒的性质、传播途径、临床表现、免疫反应机制和疫苗研究。本综述手稿旨在系统地收集、分析和总结近期有关诺如病毒的研究和调查，以加深我们对其特征和发病机制的了解。这不仅有助于后续研究人员更快、更全面地掌握诺如病毒的现有知识，也为今后的研究提供了更明确的方向和目标。

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引用次数: 0

Characterization of novel phage pK3–24 targeting multidrug-resistant Klebsiella pneumoniae and its therapeutic efficacy in Galleria mellonella larvae 针对耐多药肺炎克雷伯氏菌的新型噬菌体pK3-24的特征及其对鼠胆幼虫的疗效。

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2024-10-20 DOI: 10.1016/j.virusres.2024.199481

Junxia Feng , Xiaohu Cui , Bing Du , Jinfeng Chen , Guanhua Xue , Lin Gan , Yanling Feng , Zheng Fan , Yuehua Ke , Jinghua Cui , Tongtong Fu , Hanqing Zhao , Chao Yan , Ziying Xu , Yang Yang , Zihui Yu , Lijuan Huang , Shuo Zhao , Ziyan Tian , Zanbo Ding , Jing Yuan

Klebsiella pneumoniae is a common, conditionally pathogenic bacterium that often has a multidrug-resistant phenotype, leading to failure of antibiotic therapies. It can therefore induce serious diseases, including community-acquired pneumonia and bloodstream infections. As an emerging alternative to antibiotics, phages are considered key to solving the problem of drug-resistant bacterial infections. Here, we report a novel phage, pK3–24, that mainly targets ST447 K. pneumoniae. Phage pK3–24 is a T7-like short-tailed phage with a fast adsorption capacity that forms translucent plaques with halos on bacterial lawns. The optimal multiplicity of infection (MOI) is 0.01, and the average burst size is 50 PFU/mL. Phage pK3–24 shows environmental stability, surviving at below 50 °C and at pH values of 6–10. It has a double-stranded DNA genome of 40,327 bp and carries no antibiotic-resistance, virulence, or lysogeny genes. Phylogenetic analysis assigned phage pK3–24 to the genus Przondovirus as a new species. Phage pK3–24 inhibited the production of biofilm. Moreover, treatment with pK3–24 at doses with an MOI > 1 effectively reduced the mortality of Galleria mellonella larvae infected with ST447 K. pneumoniae.

肺炎克雷伯氏菌是一种常见的条件致病菌，通常具有耐多药表型，导致抗生素治疗失败。因此，它可能诱发严重疾病，包括社区获得性肺炎和血流感染。作为抗生素的新兴替代品，噬菌体被认为是解决耐药细菌感染问题的关键。在这里，我们报告了一种主要针对 ST447 肺炎克氏菌的新型噬菌体 pK3-24。pK3-24 是一种类似 T7 的短尾噬菌体，具有快速吸附能力，能在细菌草坪上形成带晕的半透明斑块。最佳感染倍数（MOI）为 0.01，平均迸发量为 50 PFU/mL。pK3-24 噬菌体具有环境稳定性，可在低于 50 °C 和 pH 值为 6-10 的环境中存活。它的双链 DNA 基因组为 40,327 bp，不携带抗生素抗性、毒力或溶菌基因。系统进化分析将 pK3-24 噬菌体归入 Przondovirus 属，成为一个新物种。pK3-24 噬菌体能抑制生物膜的产生。此外，以 MOI > 1 的剂量使用 pK3-24 能有效降低感染 ST447 肺炎双球菌的 Galleria mellonella 幼虫的死亡率。

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引用次数: 0

Diphyllin elicits a doubled-pronged attack on the entry of SARS-CoV-2 by inhibiting cathepsin L and furin 二氢霉素通过抑制螯合蛋白酶 L 和呋喃蛋白酶，对 SARS-CoV-2 的进入起到双管齐下的作用。

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2024-10-19 DOI: 10.1016/j.virusres.2024.199485

Binli Mao , Vu Thuy Khanh Le-Trilling , Haihuan Tang , Jie Hu , Mona S. Schmitz , Kimberly Barbet , Dan Xu , Zhen Wei , Beinu Guo , Denise Mennerich , Chun Yao , Jinxin Liu , Zhenghan Li , Yushun Wan , Xiaoyong Zhang , Kai Wang , Ni Tang , Zebo Yu , Mirko Trilling , Yong Lin

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic, posing serious threats to global health. Effective broad-spectrum antiviral drugs for the treatment of COVID-19 are not sufficiently available. In the present study, we investigated the antiviral activity of the natural lignan diphyllin (PubChem CID 100492) against different SARS-CoV-2 variants and explored the underlying molecular mechanisms. We found that diphyllin dose-dependently inhibits the SARS-CoV-2 spike (S)-mediated entry into different types of cells. The potent inhibition was evident against spike proteins derived from the original SARS-CoV-2 and from variants of concern such as Alpha, Beta, Delta or Omicron. Accordingly, diphyllin also significantly inhibited the in vitro infection of a clinical SARS-CoV-2 virus isolate. Mechanistically, diphyllin simultaneously inhibited the endosomal entry of SARS-CoV-2 by neutralizing the endosomal acidification and reducing the activity of the cysteine protease cathepsin L (CTSL) as well as S-meditated cell surface entry by impairing furin activity. Collectively, our findings establish diphyllin as novel inhibitor of CTSL and furin proteases, resulting in a double-pronged attack on SARS-CoV-2 entry along endosomal as well as cell surface routes. Therefore, diphyllin has the potential to be advanced as an inhibitor of SARS-CoV-2 entry.

严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引发了冠状病毒病 2019（COVID-19）大流行，对全球健康构成严重威胁。目前，治疗 COVID-19 的有效广谱抗病毒药物尚不充足。在本研究中，我们研究了天然木质素二氢叶黄素（PubChem CID 100492）对不同SARS-CoV-2变体的抗病毒活性，并探索了其潜在的分子机制。我们发现，Diphyllin 能剂量依赖性地抑制 SARS-CoV-2 穗状病毒（S）介导的病毒进入不同类型的细胞。这种强效抑制作用对源自原始 SARS-CoV-2 和相关变体（如 Alpha、Beta、Delta 或 Omicron）的尖峰蛋白非常明显。因此，二氢叶绿素还能显著抑制临床 SARS-CoV-2 病毒分离株的体外感染。从机理上讲，通过中和内质体酸化和降低半胱氨酸蛋白酶 cathepsin L (CTSL) 的活性，diphyllin 同时抑制了 SARS-CoV-2 的内质体进入，并通过损害呋喃蛋白酶的活性抑制了 S 介导的细胞表面进入。总之，我们的研究结果表明，diphyllin 是一种新型的 CTSL 和 furin 蛋白酶抑制剂，能双管齐下地阻止 SARS-CoV-2 沿内体和细胞表面途径进入细胞。因此，Diphyllin 有可能作为一种抑制 SARS-CoV-2 进入的药物而得到推广。

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引用次数: 0

Biology of human respiratory syncytial virus: Current perspectives in immune response and mechanisms against the virus 人类呼吸道合胞病毒生物学：目前对病毒的免疫反应和机制的看法。

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2024-10-18 DOI: 10.1016/j.virusres.2024.199483

Abayeneh Girma

Human respiratory syncytial virus (hRSV) remains a leading cause of morbidity and mortality in infants, young children, and older adults. hRSV infection's limited treatment and vaccine options significantly increase bronchiolitis' morbidity rates. The severity and outcome of viral infection hinge on the innate immune response. Developing vaccines and identifying therapeutic interventions suitable for young children, older adults, and pregnant women relies on comprehending the molecular mechanisms of viral PAMP recognition, genetic factors of the inflammatory response, and antiviral defense. This review covers fundamental elements of hRSV biology, diagnosis, pathogenesis, and the immune response, highlighting prospective options for vaccine development.

人类呼吸道合胞病毒（hRSV）仍然是婴儿、幼儿和老年人发病和死亡的主要原因。病毒感染的严重程度和结果取决于先天性免疫反应。开发疫苗和确定适合幼儿、老年人和孕妇的治疗干预措施有赖于了解病毒 PAMP 识别的分子机制、炎症反应的遗传因素和抗病毒防御。这篇综述涵盖了 hRSV 生物学、诊断、发病机理和免疫反应的基本要素，重点介绍了疫苗开发的前瞻性选择。

引用次数: 0

Genetic features of avian influenza (A/H5N8) clade 2.3.4.4b isolated from quail in Egypt 从埃及鹌鹑中分离出的禽流感（A/H5N8）2.3.4.4b 支系的遗传特征

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2024-10-17 DOI: 10.1016/j.virusres.2024.199482

Mohamed H. Elhusseiny , Moataz M. Elsayed , Wesam H. Mady , Osama Mahana , Neveen R. Bakry , Ola Abdelaziz , Abdel-Sattar Arafa , Momtaz A. Shahein , Samah Eid , Mahmoud M. Naguib

Several genotypes of the highly pathogenic avian influenza (HPAI) virus H5N8 subtype within clade 2.3.4.4b continue to circulate in different species of domestic birds across Egypt. It is believed that quail contribute to virus replication and adaptation to other gallinaceous poultry species and humans. This study provides genetic characterization of the full genome of HPAI H5N8 isolated from quail in Egypt. The virus was isolated from a commercial quail farm associated with respiratory signs. To characterize the genetic features of the detected virus, gene sequencing via Sanger technology and phylogenetic analysis were performed. The results revealed high nucleotide identity with the HPAI H5N8 virus from Egypt, which has multiple basic amino acid motifs PLREKRRKR/GLF at the hemagglutinin (HA) cleavage site. Phylogenetic analysis of the eight gene segments revealed that the quail isolate is grouped with HPAI H5N8 viruses of clade 2.3.4.4b and closely related to the most recent circulating H5N8 viruses in Egypt. Whole-genome characterization revealed amino acid preferences for avian receptors with few mutations, indicating their affinity for human-like receptors and increased virulence in mammals, such as S123P, S133A, T156A and A263T in the HA gene. In addition, the sequencing results revealed a lack of markers associated with influenza antiviral resistance in the neuraminidase and matrix-2 coding proteins. The results of the present study support the spread of HPAIV H5N8 to species other than chickens in Egypt. Therefore, continuous surveillance of AIV in different bird species in Egypt followed by full genomic characterization is needed for better virus control and prevention.

高致病性禽流感（HPAI）病毒 H5N8 亚型 2.3.4.4b 支系中的几个基因型继续在埃及各地不同种类的家禽中流行。据信，鹌鹑是病毒复制和适应其他五倍子类家禽和人类的重要因素。本研究提供了从埃及鹌鹑中分离出的高致病性禽流感 H5N8 病毒全基因组的遗传特征。该病毒是从一个出现呼吸道症状的商业鹌鹑养殖场分离出来的。为确定检测到的病毒的遗传特征，研究人员通过桑格技术进行了基因测序和系统发育分析。结果显示，该病毒与埃及高致病性禽流感 H5N8 病毒的核苷酸具有高度的一致性，后者的血凝素（HA）裂解位点有多个基本氨基酸基序 PLREKRRKR/GLF。对八个基因片段的系统进化分析表明，该鹌鹑分离物与高致病性禽流感 H5N8 病毒同属 2.3.4.4b 支系，与埃及最近流行的 H5N8 病毒关系密切。全基因组特征分析发现，该病毒的 HA 基因中的 S123P、S133A、T156A 和 A263T 等氨基酸对禽类受体具有偏好性，并有少量突变，表明其对类人受体具有亲和性，并增加了对哺乳动物的毒力。此外，测序结果显示，神经氨酸酶和基质-2 编码蛋白中缺乏与流感抗病毒性相关的标记。本研究的结果支持高致病性禽流感病毒 H5N8 在埃及向鸡以外的物种传播。因此，为了更好地控制和预防病毒，有必要对埃及不同鸟类物种中的甲型流感病毒进行持续监测，然后进行全面的基因组鉴定。

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引用次数: 0

The zoonotic LCK-3110 strain of Rocahepevirus ratti leads to mild infection in chickens after experimental inoculation 人畜共患的罗卡热病毒 LCK-3110 株在实验性接种后会导致鸡轻度感染

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2024-10-13 DOI: 10.1016/j.virusres.2024.199477

Kush Kumar Yadav , Patricia A Boley , Saroj Khatiwada , Carolyn M Lee , Menuka Bhandari , Ronna Wood , Juliette Hanson , Scott P. Kenney

Rocahepevirus ratti [rat hepatitis E virus (HEV)] was originally isolated from rats and found to be non-infectious to nonhuman primates, suggesting humans were not a susceptible host. However, in 2018, rat HEV infections were identified in human patients. High seroprevalence for rat HEV in rats in many countries necessitates studying this emerging zoonotic outbreak. Lack of a human derived rat HEV infectious clone, cell culture systems, and animal models have hindered this effort. In response to the increase in human infection cases by rat HEV, we utilized an infectious clone of the zoonotic rat HEV LCK-3110 strain originally reported from human cases. Capped RNA transcripts of the rat HEV LCK-3110 strain were synthesized, and replication was assessed in both cell culture via transfection and chickens via intrahepatic inoculation. Naive chickens were cohoused together with inoculated chickens. Our results demonstrated that although chickens were susceptible, virus replication was inefficient with only a few of the chickens inoculated with rat HEV having low levels of viremia and fecal virus shedding. However, LCK-3110 HEV was able to transmit between chickens as several naive cohoused chickens became infected as evidenced by viremia, fecal shedding, and the presence of viral protein upon histopathology of the liver. Rat HEV is an emerging zoonotic virus with an ability to spillover across species. Chickens have potential to serve as intermediary hosts, possibly playing a role in rat HEV spread and exposure to humans.

Rocahepevirus ratti[大鼠戊型肝炎病毒（HEV）]最初是从大鼠身上分离出来的，发现它对非人灵长类动物没有传染性，这表明人类不是易感宿主。然而，2018 年在人类患者中发现了大鼠 HEV 感染。在许多国家，大鼠 HEV 的血清流行率很高，因此有必要对这一新出现的人畜共患病疫情进行研究。缺乏源自人类的大鼠 HEV 感染克隆、细胞培养系统和动物模型阻碍了这项工作。为了应对大鼠 HEV 感染人类病例的增加，我们利用了最初从人类病例中报告的人畜共患大鼠 HEV LCK-3110 株的感染性克隆。我们合成了大鼠 HEV LCK-3110 株的带帽 RNA 转录本，并通过转染细胞培养和肝内接种鸡来评估其复制情况。未接种的鸡与接种的鸡同群饲养。我们的研究结果表明，虽然鸡对病毒易感，但病毒复制效率很低，只有少数接种大鼠 HEV 的鸡出现低水平的病毒血症和粪便病毒脱落。然而，LCK-3110 HEV 能够在鸡之间传播，因为几只天真的同窝鸡感染了该病毒，病毒血症、粪便脱落以及肝脏组织病理学检查中病毒蛋白的存在都证明了这一点。鼠 HEV 是一种新出现的人畜共患病毒，具有跨物种传播的能力。鸡有可能成为中间宿主，可能在大鼠 HEV 向人类传播和暴露中发挥作用。

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引用次数: 0

Human pegivirus -1 (HPgV-1) RNA frequency and genotype distribution in pediatric oncology patients with febrile neutropenia 人类疱疹病毒-1（HPgV-1）RNA 频率和基因型在患有甲状腺功能减退症的儿科临床患者中的分布。

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2024-10-11 DOI: 10.1016/j.virusres.2024.199479

Anielly Sarana da Silva , Gabriel Montenegro de Campos , Gabriela Marengone Altizani , Alice Chagas Barros , Dennis Maletich Junqueira , Simone Kashima , Sandra Coccuzzo Sampaio , Maria Carolina Elias , Marta Giovanetti , Carlos Alberto Scrideli , Svetoslav Nanev Slavov

Human Pegivirus-1, typically regarded as a commensal virus, exhibits high prevalence in humans. Its frequency and impact on oncologic pediatric patients with febrile neutropenia (FN), a frequent chemotherapy complication, remains unexplored. In this study, we assessed HPgV-1 RNA prevalence in pediatric patients experiencing FN. Blood samples were collected from 30 children, 15 presenting FN and 15 comprising a control group of either undergoing treatment or in remission. Overall, HPgV-1 RNA was detected in 23.3 % of samples (26.7 % among FN patients and 20.0 % among those under treatment or in remission). Phylogenetic analysis unveiled HPgV-1 genotype 2 predominance among these samples, the most prevalent strain circulating in Brazil. Our findings prompt crucial inquiries into the role of HPgV-1 RNA in FN: is it an incidental finding and if it can influences this clinical entity? Further investigation is imperative to elucidate HPgV-1 implications in vulnerable patients cohorts, potentially informing new approaches and understanding viral dynamics in immunocompromised populations.

人类 Pegivirus-1 通常被认为是一种共生病毒，但在人类中的流行率很高。它在儿科肿瘤患者发热性中性粒细胞减少症（FN）（一种常见的化疗并发症）中的感染频率和影响仍未得到研究。在这项研究中，我们评估了发热性中性粒细胞减少症儿科患者的 HPgV-1 RNA 感染率。我们采集了 30 名儿童的血样，其中 15 名儿童患有 FN，15 名儿童为对照组，他们要么正在接受治疗，要么病情有所缓解。总体而言，23.3%的样本中检测到了HPgV-1 RNA（FN患者为26.7%，正在接受治疗或病情缓解的患者为20.0%）。系统发育分析表明，在这些样本中，HPgV-1 基因型 2 占主导地位，是巴西流行最广的病毒株。我们的研究结果促使人们对 HPgV-1 RNA 在 FN 中的作用进行重要的探究：它是偶然发现的吗？必须进一步调查，以阐明 HPgV-1 在易感患者群中的影响，从而为新方法提供信息，并了解免疫功能低下人群中的病毒动态。

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引用次数: 0

Verteporfin is an effective inhibitor of HCMV replication Verteporfin 是一种有效的 HCMV 复制抑制剂。

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2024-10-08 DOI: 10.1016/j.virusres.2024.199475

Woo Young Lim , Ju Hyun Lee , Youngju Choi , Keejung Yoon

Human cytomegalovirus (HCMV), a double-stranded DNA virus from the Betaherpesvirinae subfamily, constitutes significant risks to newborns and immunocompromised individuals, potentially leading to severe neurodevelopmental disorders. The purpose of this study was to identify FDA-approved drugs that can inhibit HCMV replication through a drug repositioning approach. Using an HCMV progeny assay, verteporfin, a medication used as a photosensitizer in photodynamic therapy, was found to inhibit HCMV production in a dose-dependent manner, significantly reducing replication at concentrations as low as 0.5 µM, approximately 1/20th of the concentration used in anti-cancer research. Further analysis revealed that verteporfin did not interfere with HCMV host cell entry or nuclear transport but reduced viral mRNA and protein levels throughout the HCMV life cycle from the immediate-early stages. These results suggest that verteporfin has the potential to be rapidly and safely developed as a repurposed drug to inhibit HCMV infection.

人类巨细胞病毒（HCMV）是一种 Betaherpesvirinae 亚科的双链 DNA 病毒，对新生儿和免疫力低下的人构成重大风险，可能导致严重的神经发育障碍。本研究的目的是通过药物重新定位方法，找出可抑制 HCMV 复制的 FDA 批准药物。通过 HCMV 原代检测发现，在光动力疗法中用作光敏剂的药物 verteporfin 能以剂量依赖的方式抑制 HCMV 的产生，在低至 0.5 µM（约为抗癌研究所用浓度的 1/20）的浓度下就能显著减少复制。进一步的分析表明，verteporfin 不会干扰 HCMV 宿主细胞的进入或核转运，但会降低 HCMV 生命周期中从早期阶段开始的病毒 mRNA 和蛋白质水平。这些结果表明，verteporfin 有可能被快速、安全地开发为抑制 HCMV 感染的再利用药物。

引用次数: 0

Viral coexistence and insertional mutations in the ORF8 region of SARS-CoV-2: A possible mechanism of nucleotide insertion SARS-CoV-2 ORF8 区的病毒共存和插入突变：核苷酸插入的可能机制。

IF 2.5 4区医学 Q3 VIROLOGY

Virus research

Pub Date : 2024-10-05 DOI: 10.1016/j.virusres.2024.199478

Miuko Kurose , Akima Yamamoto , Abeer Mohamed Abdelfattah Elsayed , Basirat Mojisola Lawal-Ayinde , Toshihito Nomura , Akifumi Higashiura , Takashi Irie , Masaya Fukushi , Miyuki Kanda , Hidetoshi Tahara , Daichi Morita , Teruo Kuroda , Ko Ko , Kazuaki Takahashi , Junko Tanaka , Takemasa Sakaguchi

The virus obtained from a swab sample ID: S66 in Hiroshima was reported to have a single T-base insertion in the ORF8 coding region. However, no T insertion was observed when we determined the genomic sequence using another method. We then extracted RNA from the S66 swab sample and sequenced the insertion site using the Sanger method. The resulting waveform was disrupted beyond the insertion site, suggesting the presence of a mixed population of viruses with different sequences. Through plasmid cloning of RT-PCR amplification fragments and virus cloning by limiting dilution, along with TIDE analysis to determine the ratio of components from the Sanger sequencing waveform, it was confirmed that the sample contained a mixture of viruses with varying numbers of T-base insertions. The virus with one T insertion (T1+) was predominant in 70–75 % of the genomes, and genomes with T0, T2+, T3+, T4+, and T5+ were also detected. No T-base insertion mutations were observed in the ORF8 region in three other SARS-CoV-2 samples. In the S66 sample, a C27911T point mutation near the insertion site in the ORF8 region resulted in a sequence of seven or more consecutive T bases, which was the cause of the T-base insertion. When the cloned S66 virus (T1+) was passaged in cultured cells, there was a tendency for viruses with more insertion bases to become dominant with successive generations, suggesting that the T-base insertion was due to polymerase stuttering. The insertion of T bases resulted in synthesis of deletion mutants of the ORF8 protein, but no significant change was observed in the proliferation of the viruses in cultured cells. A search of the GenBank database using NCBI BLAST for viruses similar to S66 with T-base insertion mutations revealed hundreds of viruses widely distributed on the molecular phylogenetic tree. These base insertion viruses were thought to have occasionally arisen during the virus infection process. This study suggests one mechanism of insertion mutations in SARS-CoV-2, and it is important to consider the emergence of future mutant strains.

据报道，从广岛咽拭子样本（ID：S66）中获得的病毒在 ORF8 编码区有一个 T 碱基插入。然而，当我们用另一种方法测定基因组序列时，却没有发现 T 插入。随后，我们从 S66 拭子样本中提取了 RNA，并使用 Sanger 方法对插入位点进行了测序。结果发现，在插入位点之外的波形被打乱，这表明存在不同序列的混合病毒群。通过对 RT-PCR 扩增片段进行质粒克隆和用限制稀释法克隆病毒，以及用 TIDE 分析法确定 Sanger 测序波形中各成分的比例，证实样本中含有不同数量 T 碱基插入的混合病毒。有一个 T 插入（T1+）的病毒在 70-75% 的基因组中占主导地位，此外还检测到有 T0、T2+、T3+、T4+ 和 T5+ 的基因组。在另外三个 SARS-CoV-2 样本中，ORF8 区域未发现 T 碱基插入突变。在 S66 样本中，ORF8 区插入位点附近的 C27911T 点突变导致序列中出现 7 个或更多的连续 T 碱基，这就是 T 碱基插入的原因。当克隆的 S66 病毒（T1+）在培养细胞中传代时，插入碱基越多的病毒在连续几代中越显性，这表明 T 碱基插入是由于聚合酶的滞后造成的。T 碱基的插入导致 ORF8 蛋白的缺失突变体的合成，但在培养细胞中病毒的增殖方面没有观察到明显的变化。利用 NCBI BLAST 在 GenBank 数据库中搜索与 S66 相似的 T 碱基插入突变病毒，发现了数百种广泛分布在分子系统树上的病毒。这些碱基插入病毒被认为是在病毒感染过程中偶尔出现的。这项研究提出了 SARS-CoV-2 插入突变的一种机制，对考虑未来突变株的出现具有重要意义。

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引用次数: 0