{"title":"Researchers should no longer delay implementation of Pap screening in low and middle income countries pending research into novel screening approaches","authors":"Eric J Suba","doi":"10.1186/s13027-024-00576-5","DOIUrl":"https://doi.org/10.1186/s13027-024-00576-5","url":null,"abstract":"A study coordinated by Groesbeck Parham and Mark Schiffman describes a novel approach to single-visit, point-of-care cervical screening and triage for low and middle income countries (LMICs) that uses an HPV screening test that is not affordable in LMICs combined with a triage test that is not available at the point of care. Pap smears are feasible, affordable, and well-suited for single-visit, point-of-care cervical screening and triage in LMICs. Research into a discredited cervical screening test, funded by the US National Cancer Institute, contributed to at least 500,000 preventable cervical cancer deaths by delaying implementation of Pap screening throughout India for 18 years. Researchers should no longer delay implementation of Pap screening in LMICs pending research into novel screening approaches. Instead, researchers should prioritize cervical screening approaches that will save as many lives as quickly as possible in LMICs. To that end, Parham et al. should implement good-quality, single-visit, point-of-care Pap smear screening in LMICs until better-quality, single-visit, point-of-care HPV screening becomes widely affordable in LMICs.","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"1 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140803823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development and validation of a nomogram for assessing hepatocellular carcinoma risk after SVR in hepatitis C patients with advanced fibrosis and cirrhosis","authors":"Shanshan Xu, Lixia Qiu, Liang Xu, Yali Liu, Jing Zhang","doi":"10.1186/s13027-024-00578-3","DOIUrl":"https://doi.org/10.1186/s13027-024-00578-3","url":null,"abstract":"Hepatitis C patients with advanced fibrosis or cirrhosis are at high risk of developing hepatocellular carcinoma (HCC), even after sustained virological response (SVR). Clinical recommendations impose a significant burden on patients by recommending lifelong screening for HCC every six months. The goals of this study were to develop a nomogram that accurately stratifies risk of HCC and improve the screening approach that is currently in use. Risk factors for HCC were identified using univariate and multivariate analyses in this prospective study. We developed and validated a nomogram for assessing hepatocellular carcinoma risk after SVR in patients with advanced fibrosis and cirrhosis. During the median follow-up period of 61.00 (57.00–66.00) months in the derivation cohort, 37 patients (9.61%) developed HCC. Older age (HR = 1.08, 95% CI 1.02–1.14, p = 0.009), male gender (HR = 2.38, 95% CI 1.10–5.13, p = 0.027), low serum albumin levels (HR = 0.92, 95% CI 0.86–1.00, p = 0.037), and high liver stiffness measurement (LSM) (HR = 1.03, 95% CI 1.01–1.06, p = 0.001) were found to be independent predictors of HCC development. Harrell's C-index for the derivation cohort was 0.81. The nomogram’s 3-, 5- and 7-years time-dependent AUROCSs were 0.84 (95% CI 0.80–0.88), 0.83 (95% CI 0.79–0.87), and 0.81 (95% CI 0.77–0.85), respectively (all p > 0.05). According to the nomogram, patients are categorized as having low, intermediate, or high risk. The annual incidence rates of HCC in the three groups were 0.18%, 1.29%, and 4.45%, respectively (all p < 0.05). Older age, male gender, low serum albumin levels, and high LSM were risk factors for HCC after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. We used these risk factors to establish a nomogram. The nomogram can identify a suitable screening plan by classifying hepatitis C patients according to their risk of HCC.","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"14 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140803752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lixia Lu, Li Wang, Can Peng, Li Chen, Ximan He, Chenning Shao, Chunnian Wang, Rong Ge
{"title":"Undifferentiated carcinoma of the liver with osteoclast-like giant cells: a case report and literature review","authors":"Lixia Lu, Li Wang, Can Peng, Li Chen, Ximan He, Chenning Shao, Chunnian Wang, Rong Ge","doi":"10.1186/s13027-024-00582-7","DOIUrl":"https://doi.org/10.1186/s13027-024-00582-7","url":null,"abstract":"Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Osteoclast-like giant cells (OGCs) are relatively more common in pancreatic cancer, but extremely rare in HCC. Currently, there have been only a few reported cases of OGCs in HCC, and their presence indicates an aggressive clinical course. Here, we present a case of primary undifferentiated carcinoma of the liver with OGCs in a 49-year-old male patient, and through a literature review, we summarize 20 similar cases to further understand the diagnosis, treatment, and clinical course of this disease entity.","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"20 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Shen, Hao Sun, Jing Chu, Xiaodi Gong, Xiaojun Liu
{"title":"Cervicovaginal microbiota: a promising direction for prevention and treatment in cervical cancer","authors":"Jie Shen, Hao Sun, Jing Chu, Xiaodi Gong, Xiaojun Liu","doi":"10.1186/s13027-024-00573-8","DOIUrl":"https://doi.org/10.1186/s13027-024-00573-8","url":null,"abstract":"Cervical cancer is a common malignancy in women, with high incidence rate and mortality. Persistent infection of high-risk human papillomavirus (HPV) is the most important risk factor for cervical cancer and precancerous lesions. Cervicovaginal microbiota (CVM) plays an essential role in the defense of HPV infections and prevention of subsequent lesions. Dominance of Lactobacillus is the key of CVM homeostasis, which can be regulated by host, exogenous and endogenous factors. Dysbiosis of CVM, including altered microbial, metabolic, and immune signatures, can contribute to persist HPV infection, leading to cervical cancer. However, there is no evidence of the causality between CVM and cervical cancer, and the underlying mechanism remains unexplored. Considering the close correlation between CVM dysbiosis and persistent HPV infection, this review will overview CVM, its role in cervical cancer development and related mechanisms, and the prospects for therapeutic applications.","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"5 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lirong Xiao, Chaoyu Wang, Sai Ma, Yifan Wang, Liping Guan, Juyi Wu, Wei Zhang, Yao Liu, Yan Wu
{"title":"Outcome in patients with HIV-associated Hodgkin lymphoma treated with chemotherapy using Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine in the combination antiretroviral therapy (cART) era: results of a multicenter study from China","authors":"Lirong Xiao, Chaoyu Wang, Sai Ma, Yifan Wang, Liping Guan, Juyi Wu, Wei Zhang, Yao Liu, Yan Wu","doi":"10.1186/s13027-024-00571-w","DOIUrl":"https://doi.org/10.1186/s13027-024-00571-w","url":null,"abstract":"Little is known about the outcome for HIV-associated Hodgkin lymphoma (HIV-HL) as this is less common than HIV-negative lymphoma. Therefore, we performed a multi-center study to analyze the clinical characteristics and outcomes of HIV-HL patients in China. Nineteen cases of HIV-HL were diagnosed and treated at three center and including the sixth people’s hospital of Zhengzhou, Peking union medical college hospital, and Chongqing university cancer hospital, between December 2013 and June 2022. Data on the clinical features, laboratory results, response, and prognosis were collected and analyzed. The median age at diagnosis was 43(22–74) years. All patients were infected with HIV through sexual transmission, with ten cases transmitted through man having sex with man (MSM) and nine cases transmitted through heterosexual transmission. Seven patients were diagnosed with lymphoma and found to be infected with HIV. Four cases were in stage III, and fifteen cases were in stage IV. After a median follow up of 46.8(4.0-112.9) months, 17 cases were alive after ABVD regimen chemotherapy combined with combination antiretroviral therapy (cART). The 5-year progression-free survival (PFS) and overall survival (OS) rate were 83.9% and 89.5%,respectively. HIV-HL exhibits an invasive process in clinical practice, and cART combined with ABVD regimen chemotherapy can achieve long-term survival for patients.","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"52 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140600061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paolo Giorgi-Rossi, Maria Lina Tornesello, Franco Maria Buonaguro
{"title":"Why so much uncertainty about adjuvant HPV vaccines after local treatment? Can the discrepancy between the positive statistical results and the scientific community doubts be solved?","authors":"Paolo Giorgi-Rossi, Maria Lina Tornesello, Franco Maria Buonaguro","doi":"10.1186/s13027-024-00572-9","DOIUrl":"https://doi.org/10.1186/s13027-024-00572-9","url":null,"abstract":"<p>The review article <b>Can prophylactic HPV vaccination reduce the recurrence of cervical lesions after surgery? Review and prospect</b> by Han and Zhang, published on October 29, 2023, highlighted the uncertainty about the efficacy of this intervention [1]. In fact, despite several studies showing consistent results in the direction of efficacy, there is still skepticism in the scientific community about the use of the HPV vaccine as an adjuvant therapy, after local treatment, against relapses. Is there a possibility to reduce the uncertainty? To answer this question we should understand why the available evidence is inconclusive. What should be wise public health decision-making? Should the health systems recommend and pay for this intervention or not?</p><p>In this debate, we identify <b>the discrepancies between the statistical uncertainty and biological plausibility</b> as the main determinant of divergences.</p><p>Several studies have shown a protective efficacy of HPV vaccine, with consistent results ranging from 80 to 50% vaccine efficacy [2,3,4], with few exceptions showing a smaller if any, effect [5, 6]. Most of the studies were under powered [6,7,8], many of them are not randomized [7, 9] or provide indirect evidence because the vaccine was administered before treatment to already infected women [6, 10, 11], finally, the largest study was based on routinely collected data with too few clinical information to exclude major differences between the compared groups [5]. Furthermore, some studies collected different outcomes at different time points making difficult a sound meta-analysis. Nevertheless, the most recent systematic reviews [2,3,4] produced consistent estimates of vaccine efficacy for CIN2 + of 50% or more. The statistical uncertainty about the estimates was small enough to exclude the null hypothesis.</p><p>The immunological and molecular mechanisms behind the protective role of a preventive vaccine against recurrences (after local treatment) is however still a major scientific problem. The time has passed when doubts were raised about the preventive efficacy and duration of anti-HPV vaccines optimized to induce humoral immunity. However, it is now difficult to explain why such a vaccine could even prevent the lesions from recurring.</p><p>Han and Zhang, in addition to the inhibition, by anti-L1 neutralizing antibodies, of the spread of the virus from the removed infected tissue to adjacent cells and/or of new infections due to other cross-reactive HPV genotypes, reconsider the antiviral role of the microenvironment [12, 13]. The surgical intervention and the subsequent anti-inflammatory microenvironment, with a high level of cytokine secretion, could increase the efficacy of post-operative vaccination.</p><p>However, although a post-operative vaccination constitutes an effective preventive strategy for women at high risk of new infection due to their promiscuity or a possible state of immunodeficiency, protection against n","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"300 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140600769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"No detectable truncating mutations in large T antigen (LT-Ag) sequence of Merkel cell polyomavirus (MCPyV) DNA obtained from porocarcinomas.","authors":"Rosaria Arvia, Mauro Sollai, Daniela Massi, Patricia Asensio-Calavia, Carmelo Urso, Krystyna Zakrzewska","doi":"10.1186/s13027-024-00568-5","DOIUrl":"10.1186/s13027-024-00568-5","url":null,"abstract":"<p><p>Merkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma (MCC). In tumor cells the MCPyV large T antigen (LT-Ag) is frequently found truncated and this is considered a major tumor-specific signature. The role of MCPyV in other, non-MCC tumours, is little known. Viral DNA and/or tumour-specific mutations have been sometimes detected in different tumours, but such data are not unequivocal and the involvement of the virus in the tumorigenesis is not clear. In a previous study, we demonstrated a significantly higher prevalence of MCPyV DNA in formalin fixed paraffin embedded (FFPE) porocarcinoma tissues compared to the normal skin. In the present study, we investigated the presence of truncating mutations in MCPyV LT-Ag coding region in porocarcinoma specimens. Using several overlapped PCR primer pairs, the complete LT-Ag sequence from two biopsies were obtained. No truncating mutations were detected. The lack of truncating mutations in LT-Ag sequence does not seem to support the role of MCPyV in porocarcinoma oncogenesis. However, an oncogenetic mechanism, different from that proposed for MCC and not associated with the LT-Ag mutations/deletions, cannot be excluded. Further studies of more sequences coding for LT-Ag would be needed to verify this hypothesis.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"9"},"PeriodicalIF":3.7,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10956277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuyan Sheng, Bangjie Chen, Ruiyao Xu, Yanxun Han, Deshen Mao, Yuerong Chen, Conghan Li, Wenzhuo Su, Xinyang Hu, Qing Zhao, Scott Lowe, Yuting Huang, Wei Shao, Yong Yao
{"title":"A prognostic model for Schistosoma japonicum infection-associated liver hepatocellular carcinoma: strengthening the connection through initial biological experiments.","authors":"Shuyan Sheng, Bangjie Chen, Ruiyao Xu, Yanxun Han, Deshen Mao, Yuerong Chen, Conghan Li, Wenzhuo Su, Xinyang Hu, Qing Zhao, Scott Lowe, Yuting Huang, Wei Shao, Yong Yao","doi":"10.1186/s13027-024-00569-4","DOIUrl":"10.1186/s13027-024-00569-4","url":null,"abstract":"<p><strong>Background: </strong>Numerous studies have shown that Schistosoma japonicum infection correlates with an increased risk of liver hepatocellular carcinoma (LIHC). However, data regarding the role of this infection in LIHC oncogenesis are scarce. This study aimed to investigate the potential mechanisms of hepatocarcinogenesis associated with Schistosoma japonicum infection.</p><p><strong>Methods: </strong>By examining chronic liver disease as a mediator, we identified the genes contributing to Schistosoma japonicum infection and LIHC. We selected 15 key differentially expressed genes (DEGs) using weighted gene co-expression network analysis (WGCNA) and random survival forest models. Consensus clustering revealed two subgroups with distinct prognoses. Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression identified six prognostic DEGs, forming an Schistosoma japonicum infection-associated signature for strong prognosis prediction. This signature, which is an independent LIHC risk factor, was significantly correlated with clinical variables. Four DEGs, including BMI1, were selected based on their protein expression levels in cancerous and normal tissues. We confirmed BMI1's role in LIHC using Schistosoma japonicum-infected mouse models and molecular experiments.</p><p><strong>Results: </strong>We identified a series of DEGs that mediate schistosomiasis, the parasitic disease caused by Schistosoma japonicum infection, and hepatocarcinogenesis, and constructed a suitable prognostic model. We analyzed the mechanisms by which these DEGs regulate disease and present the differences in prognosis between the different genotypes. Finally, we verified our findings using molecular biology experiments.</p><p><strong>Conclusion: </strong>Bioinformatics and molecular biology analyses confirmed a relationship between schistosomiasis and liver hepatocellular cancer. Furthermore, we validated the role of a potential oncoprotein factor that may be associated with infection and carcinogenesis. These findings enhance our understanding of Schistosoma japonicum infection's role in LIHC carcinogenesis.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"10"},"PeriodicalIF":3.7,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10956344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 plasma Epstein–Barr virus DNA in posttreatment nasopharyngeal carcinoma patients after SARS-CoV-2 infection","authors":"Cheng Lin, Meifang Li, Yingying Lin, Yu Zhang, Hanchuan Xu, Bijuan Chen, Xia Yan, Yun Xu","doi":"10.1186/s13027-024-00570-x","DOIUrl":"https://doi.org/10.1186/s13027-024-00570-x","url":null,"abstract":"Nasopharyngeal carcinoma (NPC) is prevalent in southern China. EBV DNA is the most useful biomarker in NPC. However, the value of EBV DNA in posttreatment NPC patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. Sixty-four eligible NPC patients were enrolled between December 2022 and February 2023. Patients who met the following criteria were included: had non-metastatic NPC, completed radical treatment, were first firstly infected with SARS-CoV-2 and their EBV DNA changed from undetectable to detectable. At the end of follow-up, 81.25% (52/64) of patients were confirmed not to relapse with undetectable EBV DNA (no-relapse). In addition, 18.75% (12/64) of patients experienced relapse with consistent detection of EBV DNA (yes-relapse). For all 64 patients, the average time from diagnosis of coronavirus disease 2019 (COVID-19) to detection of detectable EBV DNA was 35.41 days (2 to 139 days). For 52 no-relapse patients, the average time from EBV DNA changing from detectable to undetectable was 63.12 days (6 to 147 days). The levels of EBV DNA were greater in yes-relapse patients than that in no-relapse patients, and the average of EBV DNA levels were 1216 copies/ml and 53.18 copies/ml, respectively. Using 62.3 copies/mL as the threshold, the area under the curve for EBV DNA was 0.88 for distinguishing yes-relapse patients from no-relapse patients. The sensitivity and specificity were 81.97% (95% CI 0.71–0.95) and 86.67% (95% CI 0.70–0.95), respectively. For NPC patients infected with SARS-CoV-2, EBV DNA alone is insufficient for monitoring relapse after radical therapy. Long-term follow-up and underlying mechanistic investigations of EBV DNA changes are urgently needed.","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140125724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maggie Li, Barbara J Smith, Jaeyeun Lee, Jennifer Petr, Nicole M Anders, Robyn Wiseman, Michelle A Rudek, Richard F Ambinder, Prashant J Desai
{"title":"Nelfinavir inhibition of Kaposi's sarcoma-associated herpesvirus protein expression and capsid assembly.","authors":"Maggie Li, Barbara J Smith, Jaeyeun Lee, Jennifer Petr, Nicole M Anders, Robyn Wiseman, Michelle A Rudek, Richard F Ambinder, Prashant J Desai","doi":"10.1186/s13027-024-00566-7","DOIUrl":"10.1186/s13027-024-00566-7","url":null,"abstract":"<p><strong>Background: </strong>Antiviral therapies that target herpesviruses are clinically important. Nelfinavir is a protease inhibitor that targets the human immunodeficiency virus (HIV) aspartyl protease. Previous studies demonstrated that this drug could also inhibit Kaposi's sarcoma-associated herpesvirus (KSHV) production. Our laboratory demonstrated nelfinavir can effectively inhibit herpes simplex virus type 1 (HSV-1) replication. For HSV-1 we were able to determine that virus capsids were assembled and exited the nucleus but did not mature in the cytoplasm indicating the drug inhibited secondary envelopment of virions.</p><p><strong>Methods: </strong>For KSHV, we recently derived a tractable cell culture system that allowed us to analyze the virus replication cycle in greater detail. We used this system to further define the stage at which nelfinavir inhibits KSHV replication.</p><p><strong>Results: </strong>We discovered that nelfinavir inhibits KSHV extracellular virus production. This was seen when the drug was incubated with the cells for 3 days and when we pulsed the cells with the drug for 1-5 min. When KSHV infected cells exposed to the drug were examined using ultrastructural methods there was an absence of mature capsids in the nucleus indicating a defect in capsid assembly. Because nelfinavir influences the integrated stress response (ISR), we examined the expression of viral proteins in the presence of the drug. We observed that the expression of many were significantly changed in the presence of drug. The accumulation of the capsid triplex protein, ORF26, was markedly reduced. This is an essential protein required for herpesvirus capsid assembly.</p><p><strong>Conclusions: </strong>Our studies confirm that nelfinavir inhibits KSHV virion production by disrupting virus assembly and maturation. This is likely because of the effect of nelfinavir on the ISR and thus protein synthesis and accumulation of the essential triplex capsid protein, ORF26. Of interest is that inhibition requires only a short exposure to drug. The source of infectious virus in saliva has not been defined in detail but may well be lymphocytes or other cells in the oral mucosa. Thus, it might be that a \"swish and spit\" exposure rather than systemic administration would prevent virion production.</p>","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"19 1","pages":"7"},"PeriodicalIF":3.7,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}