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Analysis of HSV1/2 Infection Reveals an Association between HSV-2 Reactivation and Pregnancy. HSV1/2感染分析揭示了HSV-2再激活与妊娠之间的关联。
IF 3.8 3区 医学 Q2 VIROLOGY Pub Date : 2024-08-28 DOI: 10.3390/v16091370
Sara Dovrat, Adar Shabat, Anat Yahav-Dovrat, Zvia Soufiev, Ella Mendelson, Ela Kashi-Zagdoun, Galia Rahav

The herpes simplex viruses consist of the strains, HSV-1 and HSV-2, which are prevalent worldwide and lack a definitive cure. We aimed to explore the specific characteristics of HSV 1 and 2 infections, such as differences between gender assigned at birth, age at infection, site of infection, comorbidities, and effect of pregnancy, through a data analysis. Between 2011 and 2018, the Israeli Central Virology Laboratory diagnosed 9189 samples using multiplexed real-time PCR. In addition, we extracted all of the medical data for 287 females hospitalized at the Sheba Medical Center with HSV-1 (161) or HSV-2 (126) genital infections. HSV-2 was almost absent in the orofacial samples from both genders, while in other lesion sites, HSV-2 was significantly more abundant in females than in males (p < 0.05,). HSV-2 was initially detected at puberty. In the hospitalized females' malignancies, both HSV-1 and HSV-2 were found with a non-significant difference. Simultaneously, pregnancies were more common in females who were HSV-2-positive compared with those who were HSV-1-positive (27.8% vs. 12.4%, respectively, p < 0.01). Primary infections occur more with HSV-1 than with HSV-2 (15.6% vs. 3.2%, respectively). Our findings demonstrate that genital HSV-2 infection episodes are more frequent during pregnancy, suggesting that pregnancy may serve as a risk factor for HSV-2 reactivation or infection.

单纯疱疹病毒由 HSV-1 和 HSV-2 株系组成,这两种病毒在全球范围内流行,目前尚无根治方法。我们旨在通过数据分析,探索 HSV 1 和 2 感染的具体特征,如出生时性别分配、感染年龄、感染部位、合并症和妊娠影响之间的差异。2011 年至 2018 年间,以色列中央病毒学实验室使用多重实时 PCR 诊断了 9189 份样本。此外,我们还提取了287名因HSV-1(161人)或HSV-2(126人)生殖器感染而在舍巴医疗中心住院的女性的所有医疗数据。在两性的口面部样本中几乎都没有发现 HSV-2,而在其他病变部位,女性的 HSV-2 感染率明显高于男性(P < 0.05)。HSV-2最初在青春期被发现。在住院的女性恶性肿瘤患者中,HSV-1 和 HSV-2 的感染率差异不大。同时,与 HSV-1 阳性的女性相比,HSV-2 阳性的女性更容易怀孕(分别为 27.8% 和 12.4%,P < 0.01)。HSV-1的原发感染率高于HSV-2(分别为15.6%对3.2%)。我们的研究结果表明,怀孕期间生殖器 HSV-2 感染的发病率更高,这表明怀孕可能是导致 HSV-2 再激活或感染的一个危险因素。
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引用次数: 0
Central and Peripheral Nervous System Manifestations Associated with Dengue Illness. 与登革热疾病相关的中枢和外周神经系统表现。
IF 3.8 3区 医学 Q2 VIROLOGY Pub Date : 2024-08-28 DOI: 10.3390/v16091367
Maria G Guzman, Eric Martinez

Dengue illness, caused by the dengue viruses, continues to be a major global health concern, with increasing incidence and the emergence of severe manifestations such as neurological complications. An overview of the current understanding of dengue epidemiology, clinical manifestations, and research priorities is presented here. Dengue transmission has escalated in recent years, exacerbated by factors such as vector expansion, climate change, and socioeconomic challenges. The clinical spectrum of dengue ranges from mild febrile illness to severe manifestations, including hemorrhagic fever and neurological complications. Neurological manifestations of dengue, once considered rare, are now increasingly reported, encompassing encephalitis, myelitis, and Guillain-Barré Syndrome, among others. Diagnosis primarily relies on laboratory methods such as RT/PCR, NS1 antigen detection, and serological assays. Despite advancements in understanding the dengue pathogenesis, there remains a critical need for effective vaccines, antiviral drugs, improved surveillance methods, predictive models for disease severity, and long-term studies on post-Dengue sequelae. Integrated programs and holistic approaches to dengue control are essential for mitigating its impact. Addressing these research priorities will be pivotal in combating dengue and reducing its global burden.

登革热病毒引起的登革热病仍然是全球关注的主要健康问题,发病率不断上升,并出现了神经系统并发症等严重表现。本文概述了目前对登革热流行病学、临床表现和研究重点的认识。近年来,登革热传播速度加快,病媒扩张、气候变化和社会经济挑战等因素加剧了登革热的传播。登革热的临床表现范围很广,从轻微的发热性疾病到严重的表现,包括出血热和神经系统并发症。登革热的神经系统表现曾被认为是罕见的,但现在有关登革热神经系统表现的报道越来越多,包括脑炎、脊髓炎和格林-巴利综合征等。诊断主要依靠 RT/PCR、NS1 抗原检测和血清学测定等实验室方法。尽管人们对登革热发病机理的认识取得了进步,但仍然迫切需要有效的疫苗、抗病毒药物、改进的监测方法、疾病严重程度预测模型以及对登革热后遗症的长期研究。控制登革热的综合计划和整体方法对于减轻登革热的影响至关重要。解决这些研究重点将是防治登革热和减轻其全球负担的关键。
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引用次数: 0
Porcine Astrovirus Infection in Brains of Pigs in Korea. 韩国猪脑中的猪 Astrovirus 感染。
IF 3.8 3区 医学 Q2 VIROLOGY Pub Date : 2024-08-28 DOI: 10.3390/v16091372
Jun-Soo Park, Chang-Gi Jeong, Su-Beom Chae, Myeon-Sik Yang, Byungkwan Oh, Sook-Young Lee, Jae-Ku Oem

Recently, neurological diseases associated with astroviruses (AstVs) have been reported in pigs, ruminants, minks, and humans. In 2017, neuro-invasive porcine astrovirus (Ni-PAstV) 3 was detected in the central nervous system (CNS) of pigs with encephalomyelitis in Hungary and the USA. In the process of diagnosing domestic pigs exhibiting neurological signs, histopathologic lesions of non-suppurative encephalomyelitis with meningitis, neuronal vacuolation, and gliosis were detected, and PAstV was identified using reverse transcriptase PCR in CNS samples of four pigs in three farms from August to September in 2020, South Korea. Subsequently, the ORF2 region was successfully acquired from three brain samples, facilitating subsequent analysis. Four genotypes of PAstV (PAstV1, 3, 4, and 5) were detected, and coinfection of PAstV with multiple genotypes was observed in brain samples. This is the first study to report Ni-PAstV infection in pigs in South Korea.

最近,在猪、反刍动物、水貂和人类中都有与星状病毒(AstVs)相关的神经系统疾病的报道。2017 年,匈牙利和美国在患有脑脊髓炎的猪的中枢神经系统(CNS)中检测到了神经侵袭性猪星状病毒(Ni-PAstV)3。在对出现神经症状的家猪进行诊断的过程中,发现了非化脓性脑脊髓炎的组织病理学病变,并伴有脑膜炎、神经元空泡化和胶质细胞病变,并在 2020 年 8 月至 9 月期间,在韩国三个农场的四头猪的中枢神经系统样本中使用逆转录酶 PCR 鉴定出 PAstV。随后,从三个脑样本中成功获得了 ORF2 区域,为后续分析提供了便利。检测到 PAstV 的四种基因型(PAstV1、3、4 和 5),并在脑样本中观察到 PAstV 与多种基因型的共感染。这是首次报告韩国猪只感染 Ni-PAstV 的研究。
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引用次数: 0
Treatment as the Best Prevention: Twice-Yearly Lenacapavir, a Game Changer in Ending the AIDS Epidemic. 治疗是最好的预防:一年两次的来那卡韦,终结艾滋病流行的改变者。
IF 3.8 3区 医学 Q2 VIROLOGY Pub Date : 2024-08-28 DOI: 10.3390/v16091368
Ziyu Wen, Minjuan Shi, Caijun Sun

Despite over four decades of unremitting efforts since the discovery of acquired immunodeficiency syndrome (AIDS)/human immunodeficiency virus (HIV), there remains no cure for HIV nor a vaccine for its prevention [...].

自后天免疫机能丧失综合症(艾滋病)/人类免疫缺陷病毒(艾滋病毒)被发现以来,尽管经过四十多年的不懈努力,仍然没有治愈艾滋病毒的方法,也没有预防艾滋病毒的疫苗[......]。
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引用次数: 0
Correction: Lopez-Gordo et al. Natural Adeno-Associated Virus Serotypes and Engineered Adeno-Associated Virus Capsid Variants: Tropism Differences and Mechanistic Insights. Viruses 2024, 16, 442. 更正:Lopez-Gordo et al:Tropism Differences and Mechanistic Insights.病毒 2024,16,442。
IF 3.8 3区 医学 Q2 VIROLOGY Pub Date : 2024-08-28 DOI: 10.3390/v16091366
Estrella Lopez-Gordo, Kyle Chamberlain, Jalish Mahmud Riyad, Erik Kohlbrenner, Thomas Weber

There was an update regarding the affiliation for Kyle Chamberlain [...].

凯尔-张伯伦的隶属关系有了最新进展[......]。
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引用次数: 0
Type I Interferonopathy among Non-Elderly Female Patients with Post-Acute Sequelae of COVID-19. 患有 COVID-19 急性后遗症的非老年女性患者中的 I 型干扰素病。
IF 3.8 3区 医学 Q2 VIROLOGY Pub Date : 2024-08-28 DOI: 10.3390/v16091369
Donghua Xu, Xuebin Qin

The pathophysiological mechanisms of the post-acute sequelae of COVID-19 (PASC) remain unclear. Sex differences not only exist in the disease severity of acute SARS-CoV-2 infection but also in the risk of suffering from PASC. Women have a higher risk of suffering from PASC and a longer time to resolution than men. To explore the possible immune mechanisms of PASC among non-elderly females, we mined single-cell transcriptome data from peripheral blood samples of non-elderly female patients with PASC and acute SARS-CoV-2 infection, together with age- and gender-matched non-PASC and healthy controls available from the Gene Expression Omnibus database. By comparing the differences, we found that a CD14+ monocyte subset characterized by higher expression of signal transducers and activators of transcription 2 (STAT2) (CD14+STAT2high) was notably increased in the PASC patients compared with the non-PASC individuals. The transcriptional factor (TF) activity analysis revealed that STAT2 and IRF9 were the key TFs determining the function of CD14+STAT2high monocytes. STAT2 and IRF9 are TFs exclusively involving type I and III interferon (IFN) signaling pathways, resulting in uncontrolled IFN-I signaling activation and type I interferonopathy. Furthermore, increased expression of common interferon-stimulated genes (ISGs) has also been identified in most monocyte subsets among the non-elderly female PASC patients, including IFI6, IFITM3, IFI44L, IFI44, EPSTI1, ISG15, and MX1. This study reveals a featured CD14+STAT2high monocyte associated with uncontrolled IFN-I signaling activation, which is indicative of a possible type I interferonopathy in the non-elderly female patients with PASC.

COVID-19 急性后遗症(PASC)的病理生理机制仍不清楚。性别差异不仅存在于急性 SARS-CoV-2 感染的疾病严重程度上,也存在于罹患 PASC 的风险上。与男性相比,女性罹患 PASC 的风险更高,且缓解时间更长。为了探索非老年女性 PASC 可能的免疫机制,我们从基因表达总库(Gene Expression Omnibus)数据库中获得了 PASC 和急性 SARS-CoV-2 感染的非老年女性患者的外周血样本,以及年龄和性别匹配的非 PASC 和健康对照组的单细胞转录组数据。通过比较两者的差异,我们发现与非 PASC 患者相比,PASC 患者的 CD14+ 单核细胞亚群中信号转导因子和转录激活因子 2(STAT2)(CD14+STAT2high)的表达明显增加。转录因子(TF)活性分析表明,STAT2 和 IRF9 是决定 CD14+STAT2high 单核细胞功能的关键 TF。STAT2和IRF9是专门参与I型和III型干扰素(IFN)信号通路的TF,导致IFN-I信号激活失控和I型干扰素病。此外,在非老年女性 PASC 患者的大多数单核细胞亚群中也发现了常见干扰素刺激基因(ISGs)的表达增加,包括 IFI6、IFITM3、IFI44L、IFI44、EPSTI1、ISG15 和 MX1。这项研究揭示了与不受控制的 IFN-I 信号激活相关的高 CD14+STAT2 单核细胞特征,这表明在非老年女性 PASC 患者中可能存在 I 型干扰素病。
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引用次数: 0
Syringe Access, Syringe Sharing, and Perceptions of HCV: A Qualitative Study Exploring the HCV Risk Environment in Rural Northern New England, United States. 注射器使用、注射器共用和对丙型肝炎病毒的认知:探索美国新英格兰北部农村地区丙型肝炎病毒风险环境的定性研究。
IF 3.8 3区 医学 Q2 VIROLOGY Pub Date : 2024-08-27 DOI: 10.3390/v16091364
Eric Romo, Elyse Bianchet, Patrick Dowd, Kathleen M Mazor, Thomas J Stopka, Peter D Friedmann

The ongoing hepatitis C virus (HCV) epidemic in the United States disproportionately affects rural people who inject drugs (PWID). This study explores the HCV risk environment in rural northern New England by examining PWID experiences and perceptions of HCV and injection equipment-sharing practices. We performed a thematic analysis on semi-structured interviews conducted with 21 adults with a history of injection drug use from rural New Hampshire, Vermont, and Massachusetts between April 2018 and August 2019. Salient themes included: (1) limited and varied access to sterile syringe sources; (2) syringe scarcity contributing to the use of informal syringe sources (e.g., secondary syringe exchange or syringe sellers who purchased syringes from out-of-state pharmacies); (3) syringe scarcity contributing to syringe sharing; (4) linkages among decisions about syringe sharing and perceptions of HCV risk, HCV status, and interpersonal trust; and (5) confusion and misconceptions about HCV, including difficulty learning one's HCV status, inadequate HCV education, and misconceptions regarding HCV transmission and treatment. Efforts to prevent and eliminate HCV among rural PWID should expand syringe access, increase awareness of HCV as a serious but preventable risk, and acknowledge social connections as potential influences on syringe access and syringe-sharing decisions.

丙型肝炎病毒(HCV)在美国的流行对农村注射吸毒者(PWID)的影响尤为严重。本研究通过考察注射吸毒者对丙型肝炎病毒(HCV)和注射设备共享做法的经历和看法,探讨了新英格兰北部农村地区的丙型肝炎病毒风险环境。我们在 2018 年 4 月至 2019 年 8 月期间对来自新罕布什尔州、佛蒙特州和马萨诸塞州农村地区的 21 名有注射吸毒史的成年人进行了半结构式访谈,并对访谈内容进行了主题分析。突出主题包括(1) 获得无菌注射器来源的途径有限且不尽相同;(2) 注射器稀缺导致使用非正规注射器来源(例如、(3) 注射器稀缺导致共用注射器;(4) 共用注射器的决定与对 HCV 风险、HCV 感染状况和人际信任的看法之间的联系;以及 (5) 对 HCV 的困惑和误解,包括难以了解自己的 HCV 感染状况、HCV 教育不足以及对 HCV 传播和治疗的误解。在农村吸毒者中预防和消除丙型肝炎病毒的工作应扩大注射器的使用范围,提高人们对丙型肝炎病毒是一种严重但可预防的风险的认识,并承认社会关系对注射器的使用和注射器共用决定具有潜在影响。
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引用次数: 0
Non-HIV Vaccine-Induced Immune Responses as Potential Baseline Immunogenicity Predictors of ALVAC-HIV and AIDSVAX B/E-Induced Immune Responses. 非艾滋病毒疫苗诱导的免疫应答作为 ALVAC-HIV 和 AIDSVAX B/E 诱导的免疫应答的潜在基线免疫原性预测因子。
IF 3.8 3区 医学 Q2 VIROLOGY Pub Date : 2024-08-27 DOI: 10.3390/v16091365
Ying Huang, Shomoita Alam, Erica Andersen-Nissen, Lindsay N Carpp, One B Dintwe, Britta S Flach, Nicole Grunenberg, Fatima Laher, Stephen C De Rosa, Guido Ferrari, Craig Innes, Linda-Gail Bekker, James G Kublin, M Juliana McElrath, Georgia D Tomaras, Glenda E Gray, Peter B Gilbert

Identifying correlations between immune responses elicited via HIV and non-HIV vaccines could aid the search for correlates of HIV protection and increase statistical power in HIV vaccine-efficacy trial designs. An exploratory objective of the HVTN 097 phase 1b trial was to assess whether immune responses [focusing on those supported as correlates of risk (CoR) of HIV acquisition] induced via the RV144 pox-prime HIV vaccine regimen correlated with those induced via tetanus toxoid (TT) and/or hepatitis B virus (HBV) vaccines. We measured TT-specific and HBV-specific IgG-binding antibody responses and TT-specific and HBV-specific CD4+ T-cell responses at multiple time points in HVTN 097 participants, and we assessed their correlations at peak time points with HIV vaccine (ALVAC-HIV and AIDSVAX B/E)-induced responses. Four correlations were significant [false discovery rate-adjusted p-value (FDR) ≤ 0.2]. Three of these four were with IgG-binding antibody responses to TT measured one month after TT receipt, with the strongest and most significant correlation [rho = 0.368 (95% CI: 0.096, 0.588; p = 0.008; FDR = 0.137)] being with IgG-binding antibody responses to MN gp120 gDneg (B protein boost) measured two weeks after the second ALVAC-HIV and AIDSVAX B/E boost. The fourth significant correlation [(rho = 0.361; 95% CI: 0.049, 0.609; p = 0.021; FDR = 0.137)] was between CD4+ T-cell responses to a hepatitis B surface antigen peptide pool, measured 2 weeks after the third HBV vaccination, and IgG-binding antibody responses to gp70BCaseAV1V2 (B V1V2 immune correlate), measured two weeks after the second ALVAC-HIV and AIDSVAX B/E boost. These moderate correlations imply that either vaccine, TT or HBV, could potentially provide a moderately useful immunogenicity predictor for the ALVAC-HIV and AIDSVAX B/E HIV vaccine regimen.

确定通过艾滋病疫苗和非艾滋病疫苗引起的免疫反应之间的相关性有助于寻找艾滋病保护的相关因素,并提高艾滋病疫苗疗效试验设计的统计能力。HVTN 097 1b 期试验的一个探索性目标是评估通过 RV144 痘痘-原液 HIV 疫苗方案诱导的免疫反应(重点是那些被支持为 HIV 感染风险相关因素 (CoR) 的免疫反应)是否与通过破伤风类毒素 (TT) 和/或乙型肝炎病毒 (HBV) 疫苗诱导的免疫反应相关。我们在多个时间点测量了 HVTN 097 参与者的 TT 特异性和 HBV 特异性 IgG 结合抗体反应以及 TT 特异性和 HBV 特异性 CD4+ T 细胞反应,并评估了它们在高峰时间点与 HIV 疫苗(ALVAC-HIV 和 AIDSVAX B/E)诱导反应的相关性。有四项相关性显著[假发现率调整 p 值 (FDR) ≤ 0.2]。其中三项与接受 TT 一个月后测量的 TT IgG 结合抗体应答相关,最强且最显著的相关性[rho = 0.368 (95% CI: 0.096, 0.588; p = 0.008; FDR = 0.137)]是与第二次 ALVAC-HIV 和 AIDSVAX B/E 增强两周后测量的 MN gp120 gDneg(B 蛋白增强)IgG 结合抗体应答相关。第四个显着相关性[(rho = 0.361; 95% CI: 0.049, 0.609; p = 0.021; FDR = 0.137)]是在第三次接种 HBV 疫苗两周后测量的 CD4+ T 细胞对乙肝表面抗原肽池的反应与第二次接种 ALVAC-HIV 和 AIDSVAX B/E 两周后测量的 IgG 结合抗体对 gp70BCaseAV1V2(B V1V2 免疫相关物)的反应。这些适度的相关性意味着,TT 或 HBV 疫苗都有可能为 ALVAC-HIV 和 AIDSVAX B/E 艾滋病毒疫苗方案提供适度有用的免疫原性预测指标。
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引用次数: 0
A Useful Method to Provide Infectious and Cultivable In Vitro Naked Viral Particles of Hepatitis A Virus. 提供具有传染性和可培养的甲型肝炎病毒体外裸病毒颗粒的有效方法。
IF 3.8 3区 医学 Q2 VIROLOGY Pub Date : 2024-08-26 DOI: 10.3390/v16091360
Gwenaëlle Verbrugghe, Chloé Soudan-Foulques, Audrey Fraisse, Prunelle Waldman Vigne, Sylvie Perelle, Fatou-Toutie Ndoye, Sandra Martin-Latil

Hepatitis A virus (HAV) is an enteric virus mainly transmitted by the faecal-oral route. Belonging to the Picornaviridae family, HAV was first described as small naked particles, like all viruses of this family. However, for about a decade, it was demonstrated that HAV particles can exist surrounded by a lipid bilayer. This type of particle, called enveloped HAV (eHAV), acquires its lipid bilayer by hijacking a part of cell membranes during the virion egress in the last steps of the viral cycle. In vitro culture systems produce mainly eHAV, and so, to date, most of the studies on HAV have been carried out using this type of viral particle. In this study, a method based on lipid bilayer removal by chemical delipidation is proposed for the production of naked HAV particles. The resulting naked HAV particles conserve their infectivity and are therefore fully cultivable in vitro. By using this method, naked HAV particles can easily be produced in vitro and can be useful to perform further studies such as inactivation processes for the food industry, as HAV is a main concern for food safety.

甲型肝炎病毒(HAV)是一种肠道病毒,主要通过粪口途径传播。HAV 属于 Picornaviridae 科,最初被描述为裸露的小颗粒,与该科的所有病毒一样。然而,大约十年后,人们发现 HAV 颗粒可以被脂质双分子层包围。这种颗粒被称为包膜 HAV(eHAV),它在病毒周期的最后几个步骤中,在病毒排出过程中劫持了部分细胞膜,从而获得了脂质双分子层。体外培养系统主要产生 eHAV,因此迄今为止,大多数有关 HAV 的研究都是使用这种病毒颗粒进行的。本研究提出了一种通过化学脱脂去除脂质双分子层的方法来生产裸 HAV 粒子。生产出的裸 HAV 颗粒保留了其感染性,因此完全可以在体外培养。使用这种方法,可以很容易地在体外生产裸 HAV 粒子,并有助于开展进一步的研究,如食品工业的灭活过程,因为 HAV 是食品安全的一个主要问题。
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引用次数: 0
Cellular N-Myristoyl Transferases Are Required for Mammarenavirus Multiplication. 细胞 N-肉豆蔻酰转移酶是乳状病毒繁殖所必需的。
IF 3.8 3区 医学 Q2 VIROLOGY Pub Date : 2024-08-26 DOI: 10.3390/v16091362
Haydar Witwit, Carlos Alberto Betancourt, Beatrice Cubitt, Roaa Khafaji, Heinrich Kowalski, Nathaniel Jackson, Chengjin Ye, Luis Martinez-Sobrido, Juan C de la Torre

The mammarenavirus matrix Z protein plays critical roles in virus assembly and cell egress. Meanwhile, heterotrimer complexes of a stable signal peptide (SSP) together with glycoprotein subunits GP1 and GP2, generated via co-and post-translational processing of the surface glycoprotein precursor GPC, form the spikes that decorate the virion surface and mediate virus cell entry via receptor-mediated endocytosis. The Z protein and the SSP undergo N-terminal myristoylation by host cell N-myristoyltransferases (NMT1 and NMT2), and G2A mutations that prevent myristoylation of Z or SSP have been shown to affect the Z-mediated virus budding and GP2-mediated fusion activity that is required to complete the virus cell entry process. In the present work, we present evidence that the validated on-target specific pan-NMT inhibitor DDD85646 exerts a potent antiviral activity against the prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV) that correlates with reduced Z budding activity and GP2-mediated fusion activity as well as with proteasome-mediated degradation of the Z protein. The potent anti-mammarenaviral activity of DDD85646 was also observed with the hemorrhagic-fever-causing Junin (JUNV) and Lassa (LASV) mammarenaviruses. Our results support the exploration of NMT inhibition as a broad-spectrum antiviral against human pathogenic mammarenaviruses.

乳腺病毒基质 Z 蛋白在病毒组装和细胞排出过程中发挥着关键作用。与此同时,稳定信号肽(SSP)与糖蛋白亚基 GP1 和 GP2 的异源三聚体复合物(通过表面糖蛋白前体 GPC 的共翻译和翻译后加工生成)形成尖峰,装饰病毒表面,并通过受体介导的内吞作用介导病毒进入细胞。Z 蛋白和 SSP 通过宿主细胞 N-肉豆蔻酰转移酶(NMT1 和 NMT2)进行 N 端肉豆蔻酰化,已证明阻止 Z 或 SSP 肉豆蔻酰化的 G2A 突变会影响 Z 介导的病毒出芽和 GP2 介导的融合活性,而这是完成病毒细胞进入过程所必需的。在本研究中,我们提出的证据表明,经过验证的靶向特异性泛 NMT 抑制剂 DDD85646 对原型哺乳动物病毒淋巴细胞性脉络膜炎病毒(LCMV)具有强效抗病毒活性,这种活性与 Z 出芽活性和 GP2 介导的融合活性降低以及蛋白酶体介导的 Z 蛋白降解相关。我们还观察到 DDD85646 对引起出血热的朱宁病毒(JUNV)和拉萨病毒(LASV)的强效抗乳腺病毒活性。我们的研究结果支持将抑制 NMT 作为抗人类致病性猛玛病毒的广谱抗病毒药物的探索。
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引用次数: 0
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