Virology Journal最新文献

{"title":"Altered LY6E and TRIM6 expression in PBMCs correlated with HBsAg clearance and response to Peg-IFN-α treatment in HBeAg-negative chronic hepatitis B patients.","authors":"Yiru Shan, Hao Pang, Yao Tang, Na Yang, Rui Wang, Fan Yang, Bo Qin","doi":"10.1186/s12985-025-02689-8","DOIUrl":"10.1186/s12985-025-02689-8","url":null,"abstract":"<p><strong>Background: </strong>Pegylated interferon alpha (Peg-IFN-α) has the potential to eradicate hepatitis B surface antigen (HBsAg). This study aimed to investigate whether the expression levels of lymphocyte antigen 6 family member E (LY6E) and tripartite motif-containing protein 6 (TRIM6) mRNAs in peripheral blood mononuclear cells (PBMCs) of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) patients is associated with the response to Peg-IFN-α treatment and HBsAg clearance.</p><p><strong>Methods: </strong>In this prospective study, HBeAg-negative chronic HBV patients treated with Peg-IFN-α were followed for 48 weeks. The participants were classified into two groups, the virological response (VR) group and nonvirological response (NVR) group, according to the changes in HBV DNA and HBsAg levels observed at week 48 of treatment. Furthermore, these patients were divided into a serological response (SR) group and a nonserological response (NSR) group, depending on whether they exhibited a loss of serum HBsAg or evidence of seroconversion. The expression levels of LY6E and TRIM6 mRNAs in PBMCs were evaluated using real-time quantitative PCR with fluorescence detection. The diagnostic performance of LY6E and TRIM6 was assessed by analyzing the receiver operating characteristic (ROC) curve and calculating the area under the ROC curve (AUC).</p><p><strong>Results: </strong>After the treatment period, the observed VR and SR rates were 44.64% and 28.57%, respectively. Dynamic changes in LY6E and TRIM6 mRNA levels were significantly different between the VR and NVR groups and between the SR and NSR groups. Multivariate analysis revealed that TRIM6 was independently associated with VR at weeks 12 and 24 of Peg-IFN-α therapy and with SR at week 12; in addition, LY6E was independently associated with VR at week 12 and SR at week 24. At week 24, the area under the curve (AUC) for LY6E in the prediction of VR was 0.6942, and the AUC for the prediction of SR was 0.7766; at week 12, TRIM6 had AUCs of 0.7600 for the prediction of VR and 0.8469 for the prediction of SR.</p><p><strong>Conclusions: </strong>LY6E and TRIM6 are important biomarkers for early therapeutic responses to Peg-IFN-α and HBsAg clearance.</p><p><strong>Trial registration: </strong>Registration number: 2023 - 311. Date of registration: 1 October 2023.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"74"},"PeriodicalIF":4.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of human papillomavirus genotypes infections in patients with cervical lesions and cervical cancer in Urumqi, Xinjiang from 2016 to 2023.","authors":"Yan Wang, Reyilanmu Maisaidi, Shihan Zhang, Yibanuer Reheman, Lili Han","doi":"10.1186/s12985-025-02674-1","DOIUrl":"10.1186/s12985-025-02674-1","url":null,"abstract":"<p><strong>Background: </strong>The persistence of high-risk human papillomavirus (HPV) infection is well-established as a key etiological factor in the progression to cervical intraepithelial neoplasia (CIN) and cervical cancer (CC). This study aims to investigate the clinical and epidemiological characteristics associated with HR-HPV infections diagnosed in conjunction with cervical intraepithelial lesions in Urumqi, Xinjiang.</p><p><strong>Methods: </strong>Between 2016 and 2023, we collected clinical data from 4,389 patients with cervical lesions who underwent colposcopic histopathological examination at the People's Hospital of Xinjiang Uygur Autonomous Region. Cervical samples were obtained for HPV DNA genotyping and cytological analysis. Patients presenting with cervical abnormalities or abnormal cytology results subsequently underwent cervical biopsy.</p><p><strong>Results: </strong>The prevalence of HPV infection among 4,389 patients with cervical lesions were found to be 98.95% (4,345/4,389). Specifically, the prevalence of HPV types 16 and 18 were 78.87% (1,314/1,666). The five most common genotypes identified were HPV types 16, 52, 58, 31, and 33, with infection rates of 34.57%, 19.54%, 12.45%, 8.98%, and 7.66%, respectively. Among the patients with cervical lesions, cervical inflammation was observed in 522 individuals (11.90%), while the distribution of cervical intraepithelial neoplasia (CIN) was as follows: CIN I in 644 patients (14.67%), CIN II in 1,067 patients (24.31%), CIN III in 1,041 patients (23.72%), and CC in 1,115 patients (25.40%). The distribution of patients in the CC group was most prevalent among those aged ≥ 60 years (47.99%, 322/671). A high prevalence was also observed in the 30~39 year age group within the CIN III group (29.47%, 275/933). Han and Uygur patients accounted for 85.90% of cervical lesion cases (3,770/4,389). Hui patients were predominantly identified within the CIN II group (34.12%), whereas Uighur patients were most frequently observed in CC group (36.60%) (P < 0.005).</p><p><strong>Conclusions: </strong>Patients with cervical lesions had high HPV prevalence in Urumqi, Xinjiang. The five most prevalent HPV types identified in this population are HPV 16, 52, 58, 31, and 33. Epidemiological studies focusing on high-risk HPV types hold significant clinical implications, particularly in informing and guiding HPV vaccination strategies.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"72"},"PeriodicalIF":4.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative analysis of serum proteomics and transcriptomics in hepatitis C.","authors":"Jianqiong Wang, Andong Xia, Min Tang, Shengjun Yang, Yandi Shen, Jinhua Dao, Rui Tao, Wei Yue","doi":"10.1186/s12985-025-02690-1","DOIUrl":"10.1186/s12985-025-02690-1","url":null,"abstract":"<p><strong>Object: </strong>Hepatitis C is a contagious disease caused by infection with the hepatitis C virus (HCV) through blood and mother-to-child routes. This study intends to characterize the serum molecular features of hepatitis C using proteomics and transcriptomics.</p><p><strong>Methods: </strong>Ctrl (normal population), HCV (population with previous HCV infection), and chronic HCV (patients with persistent HCV infection) groups were set up, and the expression profiles of the proteomes and transcriptomes of serum samples were identified using TMT and RNA-seq. Bioinformatics was applied to perform enrichment analysis and PPI network construction of differentially expressed proteins/genes (DEPs/DEGs). RT-qPCR and western blot verified the expression differences of DEPs/DEGs.</p><p><strong>Results: </strong>Compared to the Ctrl group, the HCV group had 356 DEPs in serum; compared to the HCV group, the chronic HCV group had 381 DEPs in serum. DEPs are predominantly immunoglobulins and exosomal proteins that regulate carbon dioxide transport, initiation of transcription, immune responses, and bacterial and viral infections. HSPA4, HSPD1, COPS5, PSMD2 and TCP1 are key HCV-associated proteins in DEPs. The HCV group had 684 DEGs compared to the Ctrl group, and the chronic HCV group had 350 DEGs compared to the HCV group. DEGs primarily encode the extracellular matrix and regulate wound healing, cellular communication, oxidative stress, cell adhesion, viral infection, and immunity. KIF11, CENPE, TTK, CDC20 and ASPM are HCV-related hub genes in DEGs. Combined analyses revealed interactions between DEPs and DEGs, especially EIF4A3, MNAT1, and UBE2D1. Moreover, the expression patterns of EIF4A3, EIF2B1, MNAT1, SNRNP70, and UBE2D1 in DEPs/DEGs from Ctrl, HCV, and chronic HCV groups were consistent with the sequencing results.</p><p><strong>Conclusion: </strong>EIF4A3, EIF2B1, MNAT1, SNRNP70, and UBE2D1 are involved in the process of HCV infection and pathogenesis, and they may be potential biomarkers for the treatment of patients with hepatitis C.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"73"},"PeriodicalIF":4.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiological and etiological investigation of a rare family cluster caused by severe fever with thrombocytopenia syndrome in Anhui Province in 2023.","authors":"Na Chu, Wan-Hang Lu, Xiu-Jie Chu, Jia-Bing Wu, Wei Chen, Lei Gong, Dan-Dan Song, Xiao-Wei Tan, Han-Bing Liu, Wen-Wen Liu, Yong Sun, Xiu-Zhi Chen, Ming Li, Xu-Xiang Liu","doi":"10.1186/s12985-025-02665-2","DOIUrl":"10.1186/s12985-025-02665-2","url":null,"abstract":"<p><strong>Background: </strong>Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease discovered in the 21st century. Human-to-human transmission of the disease has been documented, but the mechanisms of transmission require further investigation.</p><p><strong>Methods: </strong>Epidemiological investigations and genetic analyses of the patients were conducted, and a retrospective cohort study was performed to analyze potential risk factors for person-to-person transmission.</p><p><strong>Results: </strong>According to epidemiologic investigations, 14 secondary cases had a clear history of exposure to blood and body fluids, and 3 secondary cases may have been exposed to aerosols in a poorly ventilated environment. Risk factor assessment revealed that the risk of SFTS was 6.778 times higher [RR = 6.778, 95%CI = 1.570-29.354] among those who had direct blood contact with the indicated patient compared to those who did not, and exposure to bloody secretions from the corpse was associated with a 12.800 times higher risk for SFTS [RR = 12.800, 95%CI = 1.479-110.789] compared to contact with the blood, bloody fluids, or secretions of living patients.</p><p><strong>Conclusions: </strong>Contact with the blood of a deceased individual during funeral rites was associated with secondary cases of SFTS. The cluster outbreak is suspected to be due to person-to-person transmission of SFTSV, likely through direct contact with the blood of an SFTS patient, while the spread of aerosols in enclosed environments is also an undeniable mode of transmission.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"70"},"PeriodicalIF":4.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment and application of a wild neonatal mouse model infected with an Echovirus 30 isolate.","authors":"Ying Qu, Jing Wang, Yongbei Chen, Shengjun Xiao, Yunyi He, Ning Zhang, Huanying Zheng, Qiliang Liu, Hongbo Liu","doi":"10.1186/s12985-025-02684-z","DOIUrl":"10.1186/s12985-025-02684-z","url":null,"abstract":"<p><strong>Background: </strong>Echovirus 30 (E30) is a significant pathogen associated with various illnesses such as viral meningitis, viral myocarditis. Currently, there are no specific drugs or vaccines targeting this virus. An appropriate animal model is imperative for assessing drug and vaccine efficacy.</p><p><strong>Methods: </strong>This investigation aimed to establish a neonatal mouse model using a clinical isolate E30/A538 and apply it to screen anti-E30 drugs. The study involved evaluating the susceptibility of different mouse strains to the isolate, determining the infectious dose, transmission route, and optimal age of the mice. This model was then used to assess antiviral efficacy.</p><p><strong>Results: </strong>Neonatal ICR mice infected intracranially with 5LD₅₀ of E30/A538 at one-day-old displayed clinical symptoms such as tremors, lethargy, limb paralysis, and mortality. Importantly, the E30/A538-infected mice exhibited brain neuron apoptosis and severe myocardial necrolysis, closely resembling human infections. Elevated levels of viral RNA and positive antigen presence were predominantly detected in the brains and hearts of infected mice. Using this model to assess antiviral efficacy, it was demonstrated that interferon-α2a inhibited E30/A538 replication in vivo, mitigated histopathological changes in the brain, spinal cord, and myocardium, and enhanced the survival rate of neonatal mice.</p><p><strong>Conclusions: </strong>In summary, this research established a wild neonatal mouse model of E30/A538 isolate infection that mirrors the characteristics of human infection. The model demonstrated the efficacy of interferon-α2a in combating E30. This model would serve as a foundation for investigating the pathogenesis of E30, as well as for assessing the efficacy of vaccines and other antiviral treatments against E30.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"69"},"PeriodicalIF":4.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revolutionizing immunization: a comprehensive review of mRNA vaccine technology and applications.","authors":"Kai Yuan Leong, Seng Kong Tham, Chit Laa Poh","doi":"10.1186/s12985-025-02645-6","DOIUrl":"10.1186/s12985-025-02645-6","url":null,"abstract":"<p><p>Messenger RNA (mRNA) vaccines have emerged as a transformative platform in modern vaccinology. mRNA vaccine is a powerful alternative to traditional vaccines due to their high potency, safety, and efficacy, coupled with the ability for rapid clinical development, scalability and cost-effectiveness in manufacturing. Initially conceptualized in the 1970s, the first study about the effectiveness of a mRNA vaccine against influenza was conducted in 1993. Since then, the development of mRNA vaccines has rapidly gained significance, especially in combating the COVID-19 pandemic. Their unprecedented success during the COVID-19 pandemic, as demonstrated by the Pfizer-BioNTech and Moderna vaccines, highlighted their transformative potential. This review provides a comprehensive analysis of the mRNA vaccine technology, detailing the structure of the mRNA vaccine and its mechanism of action in inducing immunity. Advancements in nanotechnology, particularly lipid nanoparticles (LNPs) as delivery vehicles, have revolutionized the field. The manufacturing processes, including upstream production, downstream purification, and formulation are also reviewed. The clinical progress of mRNA vaccines targeting viruses causing infectious diseases is discussed, emphasizing their versatility and therapeutic potential. Despite their success, the mRNA vaccine platform faces several challenges, including improved stability to reduce dependence on cold chain logistics in transport, enhanced delivery mechanisms to target specific tissues or cells, and addressing the risk of rare adverse events. High costs associated with encapsulation in LNPs and the potential for unequal global access further complicate their widespread adoption. As the world continues to confront emerging viral threats, overcoming these challenges will be essential to fully harness the potential of mRNA vaccines. It is anticipated that mRNA vaccines will play a major role in defining and shaping the future of global health.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"71"},"PeriodicalIF":4.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization and genomic analysis of Sharanji: a jumbo bacteriophage of Escherichia coli.","authors":"Sharayu Magar, Sivaraj Barath, Debmitra Sen, Ranjith Kumar Singari, T Nagarajan, Anjali Parmar, Sutharsan Govindarajan","doi":"10.1186/s12985-025-02646-5","DOIUrl":"10.1186/s12985-025-02646-5","url":null,"abstract":"<p><strong>Background: </strong>Bacteriophages are the most genetically diverse biological entities in nature. Our current understanding of phage biology primarily stems from studies on a limited number of model bacteriophages. Jumbo phages, characterized by their exceptionally large genomes, are less frequently isolated and studied. Some jumbo phages exhibit remarkable genetic diversity, unique infection mechanisms, and therapeutic potential.</p><p><strong>Methods: </strong>In this study, we describe the isolation of Sharanji, a novel Escherichia coli jumbo phage, isolated from chicken feces. The phage genome was sequenced and analyzed extensively through gene annotation and phylogenetic analysis. The jumbo phage was phenotypically characterized through electron microscopy, host range analysis, and survival at different pH and temperatures, and one-step growth curve assay. Finally, Sharanji mediated infection of E. coli is studied through fluorescence microscopy, to analyze its mechanism of infection compared to well-studied nucleus-forming jumbo phages.</p><p><strong>Results: </strong>Whole genome sequencing reveals that Sharanji has a genome size of 350,079 bp and is a phage encompassing 593 ORFs. Genomic analysis indicates that the phage belongs to the Asteriusvirus genus and is related to E. coli jumbo phages PBECO4 and 121Q. Phenotypic analysis of isolated phage Sharanji, indicates that the phage size is 245.3 nm, and it is a narrow-spectrum phage infecting E. coli K12 strains, but not other bacteria including avian pathogenic E. coli. Infection analysis using microscopy shows that Sharanji infection causes cell filamentation. Furthermore, intracellular phage nucleus-like structures were not observed in Sharanji-infected cells, in contrast to infection by ΦKZ-like jumbo phages.</p><p><strong>Conclusions: </strong>Our study reports the isolation and characterization of Sharanji, one of the large E. coli jumbo phages. Both genotypic and phenotypic analyses suggest that Sharanji serves as a unique model system for studying phage-bacteria interactions, particularly within the context of non-nucleus-forming jumbo phages. Further exploration of jumbo phages holds promise for uncovering new paradigms in the study of microbial viruses.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"67"},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the clinical characteristics, persistent infection capability, and viral load of human papillomavirus type 82 single infection.","authors":"Zuyi Chen, Qichen Cheng, Xinyue Zhang, Feng Tao, Nana Li, Ganglin Liu, Xuejiao Mu, Mei Zhang, Zeling Dong, Qiongyao Li","doi":"10.1186/s12985-025-02688-9","DOIUrl":"10.1186/s12985-025-02688-9","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus (HPV) infection is a key factor in the development of cervical cancer and HPV genotyping is crucial for screening. There are significant differences in the pathogenic potential of the various HPV types. Currently, clinical data on HPV82 are scarce, and the relationship between its viral load, pathogenicity, and persistence is unknown. This study analyzed the characteristics of HPV82 single infection.</p><p><strong>Methods: </strong>Cervical samples were collected to determine the positivity rate of HPV82 and its clinical features in a single infection and examined the association between viral load, persistent infection, and pathogenicity.</p><p><strong>Results: </strong>The positive rate of HPV82 among women attending hospitals for gynecological physical examination or medical consultation was approximately 0.24% (1,033/435,072). Among 335 cases of HPV82 single infection, the number of patients with lesion-free tissue biopsy results, cervical intraepithelial neoplasia (CIN) 1, CIN2, CIN3, and cervical cancer were 263, 42, 11, 18, and one, respectively. A follow-up of 210 patients showed that 21.21% (7/33) of patients with CIN1 progressed to high-grade lesions, whereas 7.34% (13/177) of lesion-free patients progressed to CIN. The viral load in the CIN and cervical cancer group was significantly higher than that in the lesion-free group (p < 0.001), and the viral load in the persistent infection group was higher than that in the viral clearance group (p < 0.001).</p><p><strong>Conclusion: </strong>The pathogenicity of single HPV82 infection ranks in the middle among high-risk HPV types, and it can lead to cervical cancer, warranting the inclusion of HPV82 in expanded screening for HPV. High viral load is a significant factor that improves the persistent infection ability and pathogenicity of HPV82. Viral load is expected to serve as a screening risk factor for persistent infection and disease progression associated with HPV82.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"68"},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of single nucleotide polymorphism of IL-27P28 rs153109 and IFITM3 rs12252 on susceptibility and severity of COVID-19 in Egyptian patients: a case control study.","authors":"Hanan Hamdy, Reem H Elhamammy, Manal Abdelmageed, Ahmed Wahid","doi":"10.1186/s12985-025-02668-z","DOIUrl":"10.1186/s12985-025-02668-z","url":null,"abstract":"<p><strong>Background: </strong>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus disease 2019 (COVID-19), which is a huge global health threat. Interleukin27 (IL-27) gene is a cytokine that produces antiviral proteins in an IFN-independent manner and stimulates both pro- and anti-inflammatory responses. Interferon induced transmembrane protein 3 (IFITM3) inhibits SARS-CoV2 infection by blocking SARSCoV-2 spike proteins which facilitate viral entrance and cell-to-cell fusion. The association between genetic variants and COVID-19 in Egyptians is still unclear. Hence, we sought to investigate the impact of the single nucleotide polymorphism of IL-27P28 rs153109 and IFITM3 rs12252 on the susceptibility and severity of SARS-CoV-2 in Egyptian patients.</p><p><strong>Methods: </strong>Our study included 242 SARS-CoV-2 patients were recruited from Main University Hospital, Alexandria University, Egypt, and 187 healthy controls. We subdivided the patient group into two subgroups: group A comprised mild/moderate cases (N = 42) (17.4%), and group B included severe/critical cases (N = 200) (82.6%). Genomic DNA was extracted from blood samples using the QIAamp DNA Blood Mini kit, then the PCR products of IL27 and IFITM3 were cut by FastDigest XhoI and MScI, respectively, for detection of SNPs of IL-27P28 rs153109 (-964A/G) and IFITM3 rs12252 (T>C).</p><p><strong>Results: </strong>The present study found a significant association between IL27 rs153109 (-964A/G) and SARS-CoV-2 infection susceptibility after adjusting for the risk factor (advanced age), IL27 rs153109 (-964A/G) AG genotype (OR = 2.791, 95% CI: 1.237-6.295, P = 0.013), AA genotype (OR = 2.385, 95% CI: 1.075-5.291, P = 0.033), and (AG+AA vs. GG) genotypes (OR = 2.558, 95% CI: 1.186-5.517, P = 0.017). On the other hand, the IFITM3 rs12252(T>C) CT genotype (OR = 1.419, 95% CI: 0.843-2.391, P = 0.188), CC genotype (OR = 2.132, 95% CI: 0.436-10.415, P = 0.350), and (C/T+C/C vs. TT) genotypes (OR = 1.466, 95% CI: 0.884-2.432, P = 0.138) did not show a statistically significant association with either susceptibility or the severity of SARS-CoV-2.</p><p><strong>Conclusion: </strong>IL27P28 rs153109 AG and AA genotypes of IL27 may be associated with the susceptibility of SARS-CoV-2 infection but not the severity. Concerning the IFITM3 rs12252 SNP, we could not confirm its influence on either susceptibility or the severity of SARS-CoV-2 in this Egyptian population.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"66"},"PeriodicalIF":4.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a novel small-molecule inhibitor of the HIV-1 reverse transcriptase activity with a non-nucleoside mode of action.","authors":"Kyung-Lee Yu, YoungHyun Shin, Dong-Eun Kim, Jeong-Ah Kim, Jeong-Eun Kang, Pooja Singh, Keun Woo Lee, Chul Min Park, Hojin Kwon, Sunwoo Kim, Songmee Bae, Cheol-Hee Yoon","doi":"10.1186/s12985-025-02680-3","DOIUrl":"10.1186/s12985-025-02680-3","url":null,"abstract":"<p><strong>Background: </strong>Human immunodeficiency virus-1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome, which is a major global health problem. Although combination antiretroviral therapy (cART) successfully expands the lifespan of HIV-1-infected patients, long-term cART often increases drug resistance and adverse effects. Therefore, efforts are ongoing to develop novel anti-HIV-1 drugs.</p><p><strong>Methods: </strong>The anti-HIV-1 activities of compounds were investigated using TZM-bl reporter cell line, A3.01 T cell line, and peripheral blood mononuclear cells infected with several HIV-1 strains, including wild type and drug-resistance associated mutants. Next-generation sequencing analysis and in silico molecular docking studies were employed to determine the mode of action of the compound.</p><p><strong>Results: </strong>We identified a small-molecule inhibitor consisting of a thiadiazole core appended to two pyrazoles (BPPT), which exerted a highly potent inhibitory effect on HIV-1 infectivity, with a half-maximal effective concentration (EC₅₀) of 60 nM, without causing cytotoxicity. In experiments with various HIV-1 strains and cell types, the potency of BPPT was found to be comparable to that of commercial antiretroviral agents (azidothymidine, nevirapine, and others). Further analysis of the mode of action demonstrated that BPPT is a novel type of HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI). Analysis of viruses harboring drug-resistance-associated mutations showed that BPPT was potent against G190A (C or S) mutations in reverse transcriptase (RTase), exhibiting high-level resistance to other NNRTIs. Next-generation sequencing analysis of long-term treatment with BPPT displayed an RTase mutation profile different from that in the case of established NNRTIs. Given these data, in silico molecular docking studies demonstrated the molecular mechanism underlying the BPPT-mediated inhibition of RTase.</p><p><strong>Conclusion: </strong>Our data suggest that BPPT is a novel small-molecule inhibitor of HIV-1 RTase and could serve as a promising chemical scaffold to complement or replace conventional treatments, particularly for overcoming resistance associated with the G190 mutation.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"22 1","pages":"65"},"PeriodicalIF":4.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}