Intervirology最新文献

{"title":"HUMAN PAPILLOMAVIRUS GENOTYPE DISTRIBUTION AMONG ADULT WOMEN IN THE RABAT REGION (MOROCCO): A RETROSPECTIVE AND ANALYTICAL STUDY WITH IMPLICATIONS FOR HPV VACCINATION STRATEGIES.","authors":"Mohamed Rida Tagajdid, Sanae Azelmat, Hamza Goura, Mohamed Rida Znady, Diyae Mansouri, Rachid Abi, Hicham Elannaz, Safae Elkochri, Abdelilah Laraqui, Larbi Bouaiti, Fatima Elmengoub, Mohamed Ait Bouhou, Khalid Ennibi, Jaouad Kouach, Idriss Amine Lahlou","doi":"10.1159/int/adgag002","DOIUrl":"https://doi.org/10.1159/int/adgag002","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CC) remains a major public health challenge in Morocco, where it is the second most frequent cancer among women. Persistent infection with high-risk human papillomavirus (HR-HPV) is the primary etiological factor. Limited data exist regarding HPV genotype distribution and associated risk factors in the Moroccan female population.</p><p><strong>Methods: </strong>A retrospective, descriptive, and analytical study was conducted at the Mohammed V Military Teaching Hospital, Rabat, Morocco, between May 2023 and April 2025. Asymptomatic women aged 30-65 years undergoing routine CC screening were included. Cervical samples were collected using liquid-based cytology medium and analyzed for HR-HPV using the Cobas® 4800 assay. Samples positive for pooled HR-HPV (excluding HPV16/18) underwent extended genotyping using the HPV002® assay. Sociodemographic, behavioral, and clinical data were collected via standardized questionnaires. Statistical analysis included prevalence estimates, univariate, and multivariate logistic regression to identify factors independently associated with HR-HPV infection.</p><p><strong>Results: </strong>Of 2.235 eligible women, HR-HPV prevalence was 5.5% (n=123). HPV16 was the most prevalent genotype (19.5%), followed by HPV68 (12.2%), HPV31 (9.8%), HPV33 (7.3%), HPV35 (7.3%), and HPV39 (7.3%). Single-genotype infections predominated (95%), with dual infections in 5% of cases. Genotypes targeted by the 9-valent HPV vaccine accounted for 58.5% of infections. Multivariate analysis identified diabetes/immunosuppression, hormonal contraceptive use, and inflammatory cervical abnormalities as independent predictors of HR-HPV infection. 75% of HR-HPV-positive women were over 40 years, with a peak prevalence in the 50-59 age group.</p><p><strong>Conclusion: </strong>This study provides the first detailed characterization of HR-HPV prevalence and genotype distribution in Moroccan women attending a tertiary hospital. HPV16 remains the predominant genotype. A significant proportion of infections are preventable by the 9-valent vaccine. These findings highlight the urgent need for expanded HPV vaccination and molecular-based screening programs in Morocco and provide a critical baseline for monitoring vaccine impact and guiding public health strategies.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":" ","pages":"1"},"PeriodicalIF":1.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulated Curcumin Exerts Potent Anti-Influenza Activity by Inhibition of Akt Activation and Viral Genome Replication.","authors":"Hui-Ming Chang, Ping-Shan Lai, Cun-Zhao Li, Fong-Yuan Lin, Da-Yuan Chen, Ruei-Sheng Tsai, Shan-Chia Ou, Nianhan Ma, Wei-Li Hsu","doi":"10.1159/000552999","DOIUrl":"10.1159/000552999","url":null,"abstract":"<p><strong>Introduction: </strong>Influenza A viruses (IAVs) cause not only seasonal epidemics but also pandemics in humans. The emergence of H5N1 variants resistant to oseltamivir highlights the need to develop new antiviral therapeutic strategies. Accumulated evidence has indicated the potent anti-influenza activity of curcumin (Cur). Nevertheless, the unsatisfactory bioavailability of Cur limits its clinical use.</p><p><strong>Methods: </strong>In the present study, the anti-influenza activity and underlying mechanism of encapsulated Cur in nanoparticle form, referred to as Cur-micelle (Cur-M), were evaluated.</p><p><strong>Results: </strong>Our results demonstrated that, as with native Cur treatment, Cur-M treatment remarkably reduced IAV infection. Interestingly, Cur-M significantly inhibited IAV infectivity post-viral entry, while treatment with Cur alone showed no effect, as demonstrated by differences in plaque formation ability. By monitoring intracellular processing, including the signaling pathway required for IAV propagation and the critical viral replication step, we discovered that viral RNA replication and the activation of Akt signaling were significantly suppressed under Cur-M treatment.</p><p><strong>Conclusion: </strong>This study demonstrates for the first time that Cur-M interferes with intracellular processes required for influenza virus infection, highlighting its potential for further evaluation in both cell-based and in vivo systems.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":" ","pages":"9-20"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148225303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Tridimensional in vitro Epithelial Model of a Simulated Vaginal Environment for the Study of <i>Candida albicans</i> and Herpes Simplex Virus 2 Mono- and Coinfections.","authors":"Stefania Caramaschi, Francesco Ricchi, Arianna Sala, Laura Franceschini, Luca Fabbiani, Marzia Gozzoli, Luca Reggiani Bonetti, Elisabetta Blasi, Claudio Cermelli","doi":"10.1159/int/adgag001","DOIUrl":"10.1159/int/adgag001","url":null,"abstract":"<p><strong>Introduction: </strong>Candida albicans (C. albicans) and herpes simplex virus 2 (HSV-2) are highly prevalent genital pathogens that often coexist, potentially influencing mutual replication and host responses. Building on our recent work employing mono- and coinfections in A431 epithelial cells, we developed a three-dimensional (3D) in vitro model using inert scaffolds and the presence of a synthetic vaginal fluid (SVF) to better mimic vaginal epithelium.</p><p><strong>Methods: </strong>A431 cells were cultured on inert 3D scaffolds, with or without SVF for 5 days, and then infected with C. albicans and/or HSV-2. Cell viability was assessed by LDH release, fungal burden by CFU assay, and viral load by PCR. Histological and immunohistochemical analyses were performed to evaluate epithelial structure, pathogen presence, and IL-6 production.</p><p><strong>Results: </strong>The A431 cells formed a multilayered epithelium on scaffolds; yet, mature epithelial phenotype markers were not detected. SVF enhanced fungal growth and viral replication during coinfection. C. albicans significantly reduced epithelial viability, whereas HSV-2 showed minimal effects; dual infection caused slightly additive damage. IL-6 was produced in both mono and double infection.</p><p><strong>Conclusion: </strong>The 3D scaffold-based model supports polymicrobial infection. Nevertheless, the lack of cell epithelial phenotype highlights the need of further strategies to more closely replicate the in vivo vaginal mucosal environment.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":" ","pages":"21-33"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation of a Variant of the Felid Herpesvirus 1-Live Attenuated Vaccine Strain F2 from Unvaccinated Cats.","authors":"Yasuharu Suga, Akihiko Saito, Yasunari Kitamura, Rikio Kirisawa","doi":"10.1159/000551791","DOIUrl":"10.1159/000551791","url":null,"abstract":"<p><strong>Introduction: </strong>Felid herpesvirus 1 (FeHV-1) is widespread worldwide and is sometimes associated with chronic diseases in cats; therefore, it is clinically important. Vaccination can be used to control FeHV-1 infection. We previously isolated a strain identical to the live attenuated vaccine (LAV) strain F2 from a feline eye with a dendritic ulcer, indicating that the F2 strain may be pathogenic. The origin of the F2 strain that we previously isolated is unknown, and we surmised that the F2 strain may exist in the field. To determine whether the LAV strain F2 exists in the field, we, therefore, performed a genomic analysis of FeHV-1 isolates from cats.</p><p><strong>Methods: </strong>FeHV-1 isolates from cats were genotyped using single-nucleotide variants (SNVs) within two marker genes related to the F2 strain as indicators. Strains with markers were subjected to next-generation sequencing to determine their whole-genome sequence (WGS).</p><p><strong>Results: </strong>Of the nine FeHV-1 isolates, none were found to have two SNVs related to the F2 strain, whereas two isolates were found to have one SNV related to the F2 strain. Because the cats from which these strains were isolated lived together, the isolates were considered to be of the same strain, and we determined the WGS of one strain (strain A-19-5). All coding sequences of strain A-19-5 were identical to those of one of the cloned strains of the Merial vaccine (likely a variant of the F2 strain within the Merial vaccine population). The cat from which the strain was isolated had never received vaccination.</p><p><strong>Conclusion: </strong>The results suggest that a strain identical to a variant of the F2 strain, as found in the FeHV-1-LAV, may exist in the field.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":" ","pages":"1-8"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13229486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiviral activity of the chemokine CXCL10 against West Nile virus.","authors":"Luc Deroche, Cynthia Cavillon, Magali Garcia, Andy Larivière, Pauline Marchal, Céline Chessa, Alexia Damour, Clément Jousselin, Charles Bodet, Nicolas Lévêque","doi":"10.1159/000547037","DOIUrl":"https://doi.org/10.1159/000547037","url":null,"abstract":"<p><strong>Background: </strong>West Nile virus (WNV) is an emerging arbovirus for which there is no vaccine nor antiviral treatment. Skin cells are the primary site of WNV replication following transmission by the mosquito vector. In a previous work, strong induction of CXCL10 mRNA expression was observed during in vitro infection of human primary keratinocytes with WNV. Known to be chemoattractant, CXCL10 has also been reported to exhibit antimicrobial peptide properties through direct inhibitory activity against Gram-positive and Gram-negative bacteria. The objective of this work was to investigate the antiviral properties of CXCL10 against WNV.</p><p><strong>Methodology/principal findings: </strong>A 24-hour time-course infection of keratinocytes in the presence of CXCL10 showed a significant reduction of viral load and infectious titer in the cell culture supernatant. This inhibition of virus replication was observed when the chemokine was added to the cells before or simultaneously with the virus, suggesting pre-fusion action. In contrast, no antiviral effect was observed when CXCL10 was added 3 hours post-infection. However, incubation of the virus with CXCL10 did not show any reduction in the infectious titer, ruling out direct damage to the viral particle. In addition, expression of markers of the cells' innate immune response was not modified by adding CXCL10 during the infection. Finally, a reduction in virus attachment to the cells was demonstrated in the presence of CXCL10.</p><p><strong>Conclusion: </strong>Our results showed antiviral activity of CXCL10 against WNV during human keratinocyte infection. Even if additional experiments are required to precisely determine its mechanism of action, CXCL10 could interfere with WNV attachment to the keratinocyte surface.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":" ","pages":"1-20"},"PeriodicalIF":1.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and Antigenic Variability in VP4 and VP7 of Group A Human Rotavirus in Yunnan, China, from 2015 to 2020.","authors":"Haoyu Ma, Meifen Wang, Liufang Chuan, Shuying Long, Lijuan Qiu, Canchun Zhao, Qiangming Sun, Zhen Zhang, Hongchao Jiang","doi":"10.1159/000546065","DOIUrl":"10.1159/000546065","url":null,"abstract":"<p><strong>Background: </strong>Rotavirus (RV) A is one of the major reasons which causes acute dehydration and diarrhea. It is also one of the highest morbid diseases in children. There are only a few reports about the changes in prevalence and VP4/VP7 genotype of RVs in southwest China. Here is the report about the prevalence of RVs from 2015 to 2020 in Yunnan, southwest China.</p><p><strong>Methods: </strong>The virus genes were extracted from RV positive samples, then VP4/VP7 genes were amplified, followed by sequencing and gene typing, phylogenetic analysis, antigenic epitope variation analysis, and selective pressure analysis were also performed.</p><p><strong>Results: </strong>A total of 135 VP4 gene sequences and 143 VP7 gene sequences were obtained from stool samples during 2015-2020. Of them, P[8] genotype accounted for 97.0% of the total, while the P[4] genotype accounted for 3.0%. As for the VP7 genotype, G9 genotype accounted for 86.0% of the total, the G3 genotype accounted for 9.1%, and the G2 genotype accounted for 4.9%. G9P[8] was identified as the predominant RV strain during the epidemic season in Yunnan during 2015-2020. Phylogenetic analysis showed that G9 genotype sequences were primarily similar to African strains (KJ753473, KY661937), while P[8] genotype sequences were close to Southeast Asian strains (JQ837878, KX362594). In antigenic epitope variation analysis, among 37 epitopes of P[8] genotype, the RotaTeq™ vaccine strain covers 31 amino acid positions, Rotarix™ covers 28 amino acid positions, while LLR covers only 9. In the representative sequence of the G9 genotype, RotaTeq™ vaccine strains cover 27 out of 29 amino acid positions, Rotarix™ covers 16 positions, and LLR covers 16 positions. The results of the selective pressure analysis indicated potential positive sites for the G9P[8] genotype located at vp7-44, vp7-100, vp7-221, vp7-278, vp4-3, and vp4-4.</p><p><strong>Conclusions: </strong>Our study shows that G9P[8] is the most dominant RV genotype in Yunnan, China. Consistent with the recent epidemic trend of RV strains in China, this study could provide new perspectives on vaccine research.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":" ","pages":"43-56"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Concern.","authors":"","doi":"10.1159/000544027","DOIUrl":"10.1159/000544027","url":null,"abstract":"","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"68 1","pages":"23"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serological Evidence of Bluetongue Virus Serotypes Circulating in Pakistan.","authors":"Muhammad Ishaq, Syed Muhammad Jamal, Sakhawat Ali, Liana Teodori, Alessandra Leone, Barbara Bonfini, Massimo Spedicato, Giovanni Savini","doi":"10.1159/000546965","DOIUrl":"10.1159/000546965","url":null,"abstract":"<p><strong>Introduction: </strong>Bluetongue is an arthropod-borne viral disease of ruminants, which is caused by bluetongue virus (BTV) that exists in more than 30 different serotypes. The disease is endemic in Pakistan. However, little is known about circulating BTV serotypes in the country. This study reports the serotypes of BTV in North-Western Pakistan.</p><p><strong>Methods: </strong>A total of 758 competitive ELISA-positive serum samples were tested using serum neutralization tests against the 28 BTV serotypes (BTV-1 to BTV-27 and BTV-X). The test samples originated from cattle (n = 296), buffalo (n = 80), sheep (n = 136), and goats (n = 246).</p><p><strong>Results: </strong>Neutralizing antibodies against one or more of the 28 BTV serotypes were detected in 59.1% of the positive samples. Antibodies against BTV-26 had the highest (56.5%) prevalence, whereas, those against BTV-19 had the lowest (0.9%) prevalence. Species-wise, neutralizing antibodies against all the 28 serotypes of BTV were found in cattle, whereas antibodies against 24, 21, and 19 different serotypes of BTV were detected in goats, sheep, and buffalo, respectively. Neutralizing antibodies against 19 different BTV serotypes were detected for the first time in Pakistan. It was also the first time that neutralizing antibodies against atypical serotypes (i.e., BTV-25, BTV-27, and BTV-X) were found in cattle.</p><p><strong>Conclusion: </strong>Bluetongue in Pakistan has a complex epidemiology, as evidenced by the detection of antibodies against a large number of BTV serotypes. Findings of the current study may be helpful in selecting appropriate vaccines for control of the disease in the country.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":" ","pages":"57-66"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surveillance of Pathogens Causing Viral Diarrhea in Yichang in 2022 and 2023.","authors":"Jing Li, Zhengyuan Su, Abulimiti Moming, Jin Qian, Danna Zhang, Kangping Zhou, Yingle Liu, Bailin Liu, Kun Cai, Juan Yang","doi":"10.1159/000543907","DOIUrl":"10.1159/000543907","url":null,"abstract":"<p><strong>Introduction: </strong>This study compared the pattern of viral diarrhea in Yichang City, China, in 2022 and 2023 before and after the lifting of the COVID-19 restrictions.</p><p><strong>Methods: </strong>Stool samples were collected from outpatients and inpatients with diarrhea at three hospitals in Yichang from January to October 2022 and January to June 2023, before and after the lifting of COVID-19 restrictions, respectively. Samples were simultaneously tested for 13 types of enteric virus using a rapid multiplex assay that could simultaneously detect 13 types of five enteric viruses, including rotavirus (groups A, B, C, and H), norovirus (I, II, IV, VII, VIII, and IX), adenovirus, sapovirus, and astrovirus.</p><p><strong>Results: </strong>Testing of 458 samples showed variations in pathogen distribution by age group. Specifically, there was an increase in the number of viral infections among adults, a decrease among children, an increase in coinfection rates, and variability in virus positivity in 2023 compared to 2022.</p><p><strong>Conclusions: </strong>The multiplex assay method improved diagnostic efficiency and provided epidemiological insights. This study highlights the impact of public health transitions on viral diarrhea epidemiology, underscoring the need for ongoing surveillance and adaptable strategies in the post-COVID-19 pandemic era.</p><p><strong>Introduction: </strong>This study compared the pattern of viral diarrhea in Yichang City, China, in 2022 and 2023 before and after the lifting of the COVID-19 restrictions.</p><p><strong>Methods: </strong>Stool samples were collected from outpatients and inpatients with diarrhea at three hospitals in Yichang from January to October 2022 and January to June 2023, before and after the lifting of COVID-19 restrictions, respectively. Samples were simultaneously tested for 13 types of enteric virus using a rapid multiplex assay that could simultaneously detect 13 types of five enteric viruses, including rotavirus (groups A, B, C, and H), norovirus (I, II, IV, VII, VIII, and IX), adenovirus, sapovirus, and astrovirus.</p><p><strong>Results: </strong>Testing of 458 samples showed variations in pathogen distribution by age group. Specifically, there was an increase in the number of viral infections among adults, a decrease among children, an increase in coinfection rates, and variability in virus positivity in 2023 compared to 2022.</p><p><strong>Conclusions: </strong>The multiplex assay method improved diagnostic efficiency and provided epidemiological insights. This study highlights the impact of public health transitions on viral diarrhea epidemiology, underscoring the need for ongoing surveillance and adaptable strategies in the post-COVID-19 pandemic era.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":" ","pages":"17-22"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination Therapy with Secretome of Reovirus-Infected Mesenchymal Stem Cells and Metformin Improves Anticancer Effects of Irinotecan on Colorectal Cancer Cells in vitro.","authors":"Maliheh Elhamipour, Hoorieh Soleimanjahi, Asghar Abdoli, Negar Sharifi, Hesam Karimi, Saeed Soleyman Jahi, Ruth Kvistad","doi":"10.1159/000542356","DOIUrl":"10.1159/000542356","url":null,"abstract":"<p><strong>Introduction: </strong>Irinotecan, a topoismorase 1 inhibitor, has been used for the treatment of colorectal cancer. It was shown that monotherapy alone is largely ineffective. The combination therapy was used for antitumor activity. The synergistic anticancer effects of oncolytic reovirus-infected secretome in combination with irinotecan and metformin are evaluated in vitro. The aim of research was to assess anticancer impacts of ReoT3D, irinotecan, metformin in combination, against murine colorectal cancer cells (CT26).</p><p><strong>Methods: </strong>The L929 and the CT26 colorectal cancerous cell lines were treated in vitro with irinotecan, metformin, the Dearing strain of reovirus serotype 3 (ReoT3D) (V), and the secretome of intact (S) or reovirus-infected murine adipose-derived mesenchymal stem cells (SV). The cell viability was measured by MTT, and the apoptosis rate was analyzed by annexin V-FITC staining and flow cytometry 48 and 72 h after treatment.</p><p><strong>Results: </strong>We found that cells exposed to a combination of SV+Met+I had significantly lower cell viability and higher apoptosis rates as compared to cells exposed to Met+I, 48 and 72 h. These results suggest that metformin in combination with irinotecan and reovirus produces a synergistic effect on cell death, and adding reovirus-infected secretome (SV) to a Met+I regimen induces a higher apoptosis rate compared to Met+I alone. Based on the results, the combination of SV+Met+I has induced more apoptosis than S, SV, SV+I, and SV+Met. Also, all of the combined treatments induced apoptosis significantly versus secretome alone.</p><p><strong>Discussion: </strong>In this in vitro study, we found that the combination of T3D reovirus (oncolytic virus) and metformin with the anticancer drug irinotecan resulted in higher rates of growth inhibition and apoptosis induction in the colorectal cancer cell line. This synergistic effect was even more pronounced when using the combination of secretome derived from reovirus-infected AD-MSCs, metformin, and irinotecan.</p><p><strong>Conclusion: </strong>We highlight that the combination of ReoT3D-derived secretome with irinotecan and metformin showed a synergistic anticancer effect on the CT26 cell line, and this strategy may be considered as a new approach against colorectal cancer in the in vitro and in vivo in future studies.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":" ","pages":"1-16"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}