Viruses-Basel最新文献

{"title":"Antisera-Neutralizing Capacity of a Highly Evolved Type 2 Vaccine-Derived Poliovirus from an Immunodeficient Patient.","authors":"Yanan Wu, Runfang Zhang, Guangbo Yuan, Lingyu He, Xiaohu Dai, Hongyun Chuan, Mingqing Wang, Jing Liu, Lilan Xu, Guoyang Liao, Weidong Li, Jian Zhou","doi":"10.3390/v16111761","DOIUrl":"10.3390/v16111761","url":null,"abstract":"<p><strong>Background: </strong>The serotype 2 oral poliovirus vaccine (OPV2) can revert to regain wild-type neurovirulence and spread, causing the emergence of vaccine-derived poliovirus (VDPV2) and immunodeficiency-related vaccine-derived polioviruses (iVDPVs). In the United States, testing carried out by the CDC of type II iVDPV (iVDPV2) with human immune serum from the vaccine has shown that the presence of the virus poses a threat to eradication efforts.</p><p><strong>Methods: </strong>We analyzed the major neutralization sites of VP1, VP2, and VP3 of the iVDPV using bioinformatics techniques and homology modeling (SWISS-MODEL). The three amino acid residues 679, 680, and 141 of the P1 region changed, which had an impact on the spatial conformation of the viral-neutralizing site. We tested polio-vaccinated human sera and rabbit anti-Sabin II polyantibodies against a panel of iVDPV pseudoviruses.</p><p><strong>Results: </strong>The results demonstrated that the serum's capacity to neutralize mutant pseudoviruses diminished when amino acid substitutions were introduced into the P1 encapsidated protein, particularly when 141 and 679 were mutated together. This study emphasizes the significance of continually monitoring individuals who are known to be immunocompromised and maintaining high vaccination rates in OPV-using communities.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733989","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":"Self-Replicating Alphaviruses: From Pathogens to Therapeutic Agents.","authors":"Kenneth Lundstrom","doi":"10.3390/v16111762","DOIUrl":"10.3390/v16111762","url":null,"abstract":"<p><p>Alphaviruses are known for being model viruses for studying cellular functions related to viral infections but also for causing epidemics in different parts of the world. More recently, alphavirus-based expression systems have demonstrated efficacy as vaccines against infectious diseases and as therapeutic applications for different cancers. Point mutations in the non-structural alphaviral replicase genes have generated enhanced transgene expression and created temperature-sensitive expression vectors. The recently engineered trans-amplifying RNA system can provide higher translational efficiency and eliminate interference with cellular translation. The self-replicating feature of alphaviruses has provided the advantage of extremely high transgene expression of vaccine-related antigens and therapeutic anti-tumor and immunostimulatory genes, which has also permitted significantly reduced doses for prophylactic and therapeutic applications, potentially reducing adverse events. Furthermore, alphaviruses have shown favorable flexibility as they can be delivered as recombinant viral particles, RNA replicons, or DNA-replicon-based plasmids. In the context of infectious diseases, robust immune responses against the surface proteins of target agents have been observed along with protection against challenges with lethal doses of infectious agents in rodents and primates. Similarly, the expression of anti-tumor genes and immunostimulatory genes from alphavirus vectors has provided tumor growth inhibition, tumor regression, and cures in animal cancer models. Moreover, protection against tumor challenges has been observed. In clinical settings, patient benefits have been reported. Alphaviruses have also been considered for the treatment of neurological disorders due to their neurotrophic preference.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734034","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":"Protective Role of Cepharanthine Against Equid Herpesvirus Type 8 Through AMPK and Nrf2/HO-1 Pathway Activation.","authors":"Shuwen Li, Liangliang Li, Yijia Sun, Muhammad Zahoor Khan, Yue Yu, Lian Ruan, Li Chen, Juan Zhao, Junchi Jia, Yubao Li, Changfa Wang, Tongtong Wang","doi":"10.3390/v16111765","DOIUrl":"10.3390/v16111765","url":null,"abstract":"<p><p>Equid herpesvirus type 8 (EqHV-8) is known to cause respiratory disease and miscarriage in horses and donkeys, which is a major problem for the equine farming industry. However, there are currently limited vaccines or drugs available to effectively treat EqHV-8 infection. Therefore, it is crucial to develop new antiviral approaches to prevent potential pandemics caused by EqHV-8. This study evaluates the antiviral and antioxidant effects of cepharanthine against EqHV-8 by employing both in vitro assays and in vivo mouse models to assess its therapeutic efficacy. To assess the effectiveness of cepharanthine against EqHV-8, we conducted experiments using NBL-6 and RK-13 cells. Additionally, we developed a mouse model to validate cepharanthine's effectiveness against EqHV-8. In our in vitro experiments, we assessed the cepharanthine's ability to inhibit infection caused by EqHV-8 in NBL-6 and RK-13 cells. Our results demonstrated that cepharanthine has a dose-dependent inhibitory effect, indicating that it possesses anti-EqHV-8 properties at the cellular level. Moreover, we investigated the mechanism through which cepharanthine exerts its protective effects. It was observed that cepharanthine effectively reduces the oxidative stress induced by EqHV-8 by activating the AMPK and Nrf2/HO-1 signaling pathways. Furthermore, when administered to EqHV-8 infected mice, cepharanthine significantly improved lung tissue pathology and reduced oxidative stress. The findings presented herein collectively highlight cepharanthine as a promising candidate for combating EqHV-8 infections.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733792","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":"A Pilot Randomised Controlled Trial Involving Financial Incentives to Facilitate Hepatitis C Treatment Uptake Among People Who Inject Drugs: ETHOS Engage Study.","authors":"Alison D Marshall, Anna Conway, Evan B Cunningham, Heather Valerio, David Silk, Maryam Alavi, Shane Tillakeratne, Alexandra Wade, Thao Lam, Krista Zohrab, Adrian Dunlop, Craig Connelly, Victoria Cock, Carina Burns, Charles Henderson, Michael Christmass, Gregory J Dore, Jason Grebely","doi":"10.3390/v16111763","DOIUrl":"10.3390/v16111763","url":null,"abstract":"<p><p>The primary aim of this study was to establish the feasibility of implementing a larger RCT designed to evaluate the effect of financial incentives on HCV treatment initiation among persons receiving opioid agonist therapy and/or who have injected drugs in the prior six months. ETHOS Engage is an observational cohort of participants recruited from drug treatment and needle and syringe programs in Australia. Among 11 drug and alcohol clinics, participants who were HCV RNA-positive were randomized (1:1) to receive standard of care or a AUD $60 gift card at treatment initiation. Regarding feasibility, 100% (57/57) of eligible participants enrolled to take part. Twenty-eight participants were randomised to the financial incentive arm (AUD $60 gift card) plus standard of care and 29 participants to the standard of care arm. In this pilot RCT (n = 57), median age was 42 years (IQR 37-49), 63% were male (n = 36), 35% Indigenous (n = 20) and 36% (n = 21) reported injecting drugs daily in the past month. Twelve weeks post-study enrolment, 11 (39%) participants in the financial incentive arm and 17 (59%) participants in the standard of care arm initiated HCV treatment. Findings indicate high feasibility among people who inject drugs to be randomised to receive financial incentives to initiate HCV treatment.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733961","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":"The Emergence of Saliva as a Diagnostic and Prognostic Tool for Viral Infections.","authors":"Nilson Ferreira de Oliveira Neto, Rafael Antônio Velôso Caixeta, Rodrigo Melim Zerbinati, Amanda Caroline Zarpellon, Matheus Willian Caetano, Debora Pallos, Roger Junges, André Luiz Ferreira Costa, Juan Aitken-Saavedra, Simone Giannecchini, Paulo Henrique Braz-Silva","doi":"10.3390/v16111759","DOIUrl":"10.3390/v16111759","url":null,"abstract":"<p><p>Saliva has emerged as a promising diagnostic fluid for viral infections, enabling the direct analysis of viral genetic material and the detection of infection markers such as proteins, metabolites, microRNAs, and immunoglobulins. This comprehensive review aimed to explore the use of saliva as a diagnostic tool for viral infections, emphasizing its advantages and limitations. Saliva stands out due to its simplicity and safety in collection, along with the convenience of self-collection without the need for healthcare supervision, while potentially being comparable to urine and blood in terms of effectiveness. Herein, we highlighted the significant potential of saliva in assessing viral loads and diagnosing viral infections, such as herpesviruses, HPV, PyV, TTV, SARS-CoV-2, and MPXV. The detection of viral shedding in saliva underscores its utility in early diagnosis, the monitoring of infection progression, and evaluating treatment responses. The non-invasive nature of saliva collection makes it an appealing alternative to more invasive methods, promoting better patient compliance and facilitating large-scale screening and surveillance. As such, we further highlight current evidence on the use of saliva as a prognostic tool. Although a significant amount of data is already available, further investigations are warranted to more comprehensively assess the added benefit from the utilization of salivary biomarkers in the clinics. Salivary biomarkers show great promise for the early detection and prevention of viral infection complications, potentially improving disease management and control at the population level. Integrating these non-invasive tools into routine clinical practice could enhance personalized healthcare strategies and patient outcomes. Future studies should focus on establishing standardization protocols, validating the accuracy of salivary diagnostics, and expanding clinical research to enhance the diagnostic and monitoring capabilities of salivary biomarkers.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734201","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":"The Apparent Lack of the Risk of Intussusception Immediately After Rotavirus Vaccination Among Japanese Infants.","authors":"Wakako Kikuchi, Atsuko Noguchi, Yoko Sato, Yuuki Konno, Akira Komatsu, Satoru Tandai, Wataru Kikuchi, Shinobu Miura, Hiroshi Fukaya, Tomoaki Ohata, Hiroo Noguchi, Kenichi Matsuno, Hisayuki Tsukahara, Daiki Kondo, Masaki Komatsu, Masamichi Tamura, Hiromi Koizumi, Toyoko Nakagomi, Osamu Nakagomi, Tsutomu Takahashi","doi":"10.3390/v16111758","DOIUrl":"10.3390/v16111758","url":null,"abstract":"<p><p>Rotavirus vaccines carry a small risk of intussusception mainly 1-7 days after vaccination in the United States of America, Europe, Australia, and Latin America where the background rate of intussusception is relatively low. Such risks are undetectable in Africa and India where the background rate is the lowest. Because few studies were carried out in high-background-rate countries such as Japan, we examined how intussusception occurred in infants living in Akita prefecture, Japan, while the vaccines were sold in the private market. Between 2011 and 2018, an estimated 21,677 infants (46%) were vaccinated and 54% were not. Through a retrospective survey of medical records in 18 hospitals in the prefecture, we identified 58 infants, 28 of whom were vaccinated and 30 of whom were unvaccinated, as having intussusception that met level 1 of the Brighton criteria. Thus, the intussusception rate was 123 per 100,000 infant-years (95% confidence interval [CI]: 94-160). Despite the high rate, none developed intussusception 1-7 days after the first dose of either the monovalent human rotavirus vaccine (GSK) or the pentavalent human-bovine reassortant vaccine (MSD). The incidence rate ratio of vaccinated to unvaccinated infants between 42 and 245 days of life was estimated at 0.96 (95%CI: 0.43-2.1; <i>p</i> = 0.92). Given that over 95% of infants received the first dose before 15 weeks of age, the risk of intussusception associated with the rotavirus vaccines in high-incidence-rate countries can be reduced to a minimum by adhering to the recommended schedule at 2, 3, and 4 months of age.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734155","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":"Application of a Sensitive Capture Sequencing Approach to Reservoir Surveillance Detects Novel Viruses in Zambian Wild Rodents.","authors":"Lavel C Moonga, Jones Chipinga, John P Collins, Vishal Kapoor, Ngonda Saasa, King S Nalubamba, Bernard M Hang'ombe, Boniface Namangala, Tapiwa Lundu, Xiang-Jun Lu, Samuel Yingst, J Kenneth Wickiser, Thomas Briese","doi":"10.3390/v16111754","DOIUrl":"10.3390/v16111754","url":null,"abstract":"<p><p>We utilized a pan-viral capture sequencing assay, VirCapSeq-VERT, to assess viral diversity in rodents from the Eastern Province of Zambia as a model for pre-pandemic viral reservoir surveillance. We report rodent adeno-, parvo-, paramyxo-, and picornaviruses that represent novel species or isolates, including murine adenovirus 4, two additional species in the genus <i>Chaphamaparvovirus</i>, two paramyxoviruses distantly related to unclassified viruses in the genus <i>Jeilongvirus</i>, and the first <i>Aichivirus A</i> sequence identified from rodents in Africa. Our results emphasize the importance of rodents as a reservoir for potential zoonotic viruses.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733994","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":"The Polypyrimidine Tract-Binding Protein Is a Transacting Factor for the Dengue Virus Internal Ribosome Entry Site.","authors":"Leandro Fernández-García, Jenniffer Angulo, Marcelo López-Lastra","doi":"10.3390/v16111757","DOIUrl":"10.3390/v16111757","url":null,"abstract":"<p><p><i>Dengue virus</i> (DENV) is an enveloped, positive sense, single-stranded RNA virus belonging to the <i>Flaviviridae</i>. Translation initiation of the DENV mRNA (vRNA) can occur following a cap-dependent, 5'-3'end-dependent internal ribosome entry site (IRES)-independent or IRES-dependent mechanism. This study evaluated the activity of DENV IRES in BHK-21 cells and the role of the polypyrimidine-tract binding protein (PTB) isoforms PTB1, PTB2, and PTB4 as IRES-transacting factors (ITAFs) for the DENV IRES. The results show that DENV-IRES activity is stimulated in DENV-replicating BHK-21 cells and cells expressing the <i>Foot-and-mouth disease virus</i> leader or <i>Human rhinovirus</i> 2A proteases. Protease activity was necessary, although a complete shutdown of cap-dependent translation initiation was not a requirement to stimulate DENV IRES activity. Regarding PTB, the results show that PTB1 > PTB2 > PTB4 stimulates DENV-IRES activity in BHK-21 cells. Mutations in the PTB RNA recognition motifs (RRMs), RRM1/RRM2 or RRM3/RRM4, differentially impact PTB1, PTB2, and PTB4's ability to promote DENV IRES-mediated translation initiation in BHK-21 cells. PTB1-induced DENV-IRES stimulation is rescinded when RRM1/RRM2 or RRM3/RRM4 are disrupted. Mutations in RRM1/RRM2 or RRM3/RRM4 do not affect the ITAF activity of PTB2. Mutating RRM3/RRM4, but not RRM1/RRM2, abolishes the ability of PTB4 to stimulate the DENV IRES. Thus, PTB1, PTB2, and PTB4 are ITAFs for the DENV IRES.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734233","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 HTLV-1 Infectious Molecular Clone Isolated from Patient with HAM/TSP and Immortalization of Human Primary T-Cell Lines.","authors":"Marcia Bellon, Pooja Jain, Christophe Nicot","doi":"10.3390/v16111755","DOIUrl":"10.3390/v16111755","url":null,"abstract":"<p><p>Human T-cell leukemia virus (HTLV-1) is the etiological agent of lymphoproliferative diseases such as adult T-cell leukemia and T-cell lymphoma (ATL) and a neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). While several molecular clones of HTLV-1 have been published, all were isolated from samples derived from patients with adult T-cell leukemia. Here, we report the characterization of an HTLV-1 infectious molecular clone isolated from a sample of a patient with HAM/TSP disease. Genetic comparative analyses of the HAM/TSP molecular clone (pBST) revealed unique genetic alterations and specific viral mRNA expression patterns. Interestingly, our clone also harbors characteristics previously published to favor the development of HAM/TSP disease. The molecular clone is capable of infection and immortalization of human primary T cells in vitro. Our studies further demonstrate that the HTLV-1 virus produced from primary T cells transfected with pBST or ACH molecular clones cannot sustain long-term expansion, and cells cease to proliferate after 3-4 months in culture. In contrast, long-term proliferation and immortalization were achieved if the virus was transmitted from dendritic cells to primary T cells, and secondary infection of 729B cells in vitro was demonstrated. In both primary T cells and 729B cells, pBST and ACH were latent, and only <i>hbz</i> viral RNA was detected. This study suggests that HTLV-1 transmission from DC to T cells favors the immortalization of latently infected cells.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734021","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":"piRNA Defense Against Endogenous Retroviruses.","authors":"Milky Abajorga, Leonid Yurkovetskiy, Jeremy Luban","doi":"10.3390/v16111756","DOIUrl":"10.3390/v16111756","url":null,"abstract":"<p><p>Infection by retroviruses and the mobilization of transposable elements cause DNA damage that can be catastrophic for a cell. If the cell survives, the mutations generated by retrotransposition may confer a selective advantage, although, more commonly, the effect of new integrants is neutral or detrimental. If retrotransposition occurs in gametes or in the early embryo, it introduces genetic modifications that can be transmitted to the progeny and may become fixed in the germline of that species. PIWI-interacting RNAs (piRNAs) are single-stranded, 21-35 nucleotide RNAs generated by the PIWI clade of Argonaute proteins that maintain the integrity of the animal germline by silencing transposons. The sequence specific manner by which piRNAs and germline-encoded PIWI proteins repress transposons is reminiscent of CRISPR, which retains memory for invading pathogen sequences. piRNAs are processed preferentially from the unspliced transcripts of piRNA clusters. Via complementary base pairing, mature antisense piRNAs guide the PIWI clade of Argonaute proteins to transposon RNAs for degradation. Moreover, these piRNA-loaded PIWI proteins are imported into the nucleus to modulate the co-transcriptional repression of transposons by initiating histone and DNA methylation. How retroviruses that invade germ cells are first recognized as foreign by the piRNA machinery, as well as how endogenous piRNA clusters targeting the sequences of invasive genetic elements are acquired, is not known. Currently, koalas (<i>Phascolarctos cinereus)</i> are going through an epidemic due to the horizontal and vertical transmission of the KoRV-A gammaretrovirus. This provides an unprecedented opportunity to study how an exogenous retrovirus becomes fixed in the genome of its host, and how piRNAs targeting this retrovirus are generated in germ cells of the infected animal. Initial experiments have shown that the unspliced transcript from KoRV-A proviruses in koala testes, but not the spliced KoRV-A transcript, is directly processed into sense-strand piRNAs. The cleavage of unspliced sense-strand transcripts is thought to serve as an initial innate defense until antisense piRNAs are generated and an adaptive KoRV-A-specific genome immune response is established. Further research is expected to determine how the piRNA machinery recognizes a new foreign genetic invader, how it distinguishes between spliced and unspliced transcripts, and how a mature genome immune response is established, with both sense and antisense piRNAs and the methylation of histones and DNA at the provirus promoter.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733646","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}