Current topics in microbiology and immunology最新文献

{"title":"Common Features Between Stroke Following Varicella in Children and Stroke Following Herpes Zoster in Adults : Varicella-Zoster Virus in Trigeminal Ganglion.","authors":"Charles Grose, Amir Shaban, Heather J Fullerton","doi":"10.1007/82_2021_236","DOIUrl":"10.1007/82_2021_236","url":null,"abstract":"<p><p>The cerebral arteries are innervated by afferent fibers from the trigeminal ganglia. Varicella-zoster virus (VZV) frequently resides in the trigeminal ganglion. Reports of arterial ischemic stroke due to VZV cerebral vasculopathy in adults after herpes zoster have been described for decades. Reports of arterial ischemic stroke due to post-varicella cerebral arteriopathy in children have also been described for decades. One rationale for this review has been post-licensure studies that have shown an apparent protective effect from stroke in both adults who have received live zoster vaccine and children who have received live varicella vaccine. In this review, we define common features between stroke following varicella in children and stroke following herpes zoster in adults. The trigeminal ganglion and to a lesser extent the superior cervical ganglion are central to the stroke pathogenesis pathway because afferent fibers from these two ganglia provide the circuitry by which the virus can travel to the anterior and posterior circulations of the brain. Based on studies in pseudorabies virus (PRV) models, it is likely that VZV is carried to the cerebral arteries on a kinesin motor via gE, gI and the homolog of PRV US9. The gE product is an essential VZV protein.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":"247-272"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39158090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of Apoptosis and Cell Death Pathways by Varicella-Zoster Virus.","authors":"M. Steain, B. Slobedman, A. Abendroth","doi":"10.1007/82_2021_249","DOIUrl":"https://doi.org/10.1007/82_2021_249","url":null,"abstract":"","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45303121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humanized Severe Combined Immunodeficient (SCID) Mouse Models for Varicella-Zoster Virus Pathogenesis.","authors":"M. Lloyd, J. Moffat","doi":"10.1007/82_2022_255","DOIUrl":"https://doi.org/10.1007/82_2022_255","url":null,"abstract":"","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43253585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Development of mRNA Vaccines: Challenges and Opportunities.","authors":"Allison August,&nbsp;Luis Brito,&nbsp;Robert Paris,&nbsp;Tal Zaks","doi":"10.1007/82_2022_259","DOIUrl":"https://doi.org/10.1007/82_2022_259","url":null,"abstract":"<p><p>The emergence of safe and effective mRNA platform-based COVID-19 vaccines from the recent pandemic has changed the face of vaccine development. Compared with conventional technologies used historically, mRNA-based vaccines offer a rapid flexible and robust approach to preventing disease caused by transient viral strains such as SAR2-CoV-2 variants of concern and seasonal influenza. Adaptations in the formulation of the mRNA delivery systems such as with lipid nanoparticle delivery (LNP) used in mRNA-1273 and BNT16b2b have enabled this technology to flourish under the urgent collective response and collaborative regulatory understanding derived from COVID-19 vaccine development. The application of mRNA-based therapeutics in other areas holds potential promise including combination vaccines that might deliver protections against multiple infectious diseases. Future studies and further advances in mRNA-based technologies will provide insight into the clinical efficacy and real-world effectiveness of vaccines as well as provisions with respect to the impact of reactogenicity profiles. Overall, the success of mRNA-based COVID-19 vaccines has helped unlock a platform likely to result in many more candidate vaccines entering clinical evaluation to address the unmet medical needs of other diseases including viral respiratory diseases, herpesviruses, and historically challenging vaccine targets such as HIV.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":"440 ","pages":"167-186"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10868067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing PI3K Inhibitors for Respiratory Diseases.","authors":"E Fagone,&nbsp;M Fruciano,&nbsp;E Gili,&nbsp;G Sambataro,&nbsp;Carlo Vancheri","doi":"10.1007/978-3-031-06566-8_19","DOIUrl":"https://doi.org/10.1007/978-3-031-06566-8_19","url":null,"abstract":"<p><p>A number of different experimental models using both non-selective and selective PI3K inhibitors have shown that many pathogenic steps of respiratory disorders, such as bronchial asthma, Chronic Obstructive Pulmonary Disease (COPD), Idiopathic Pulmonary Fibrosis (IPF), Acute Respiratory Distress Syndrome (ARDS) and Lung Cancer (LC) are, at least in part, regulated by the PI3K signaling pathway, suggesting that the inhibition of PI3K could represent an ideal therapeutic target for the treatment of respiratory diseases. This chapter summarizes the current state of the therapeutic strategies aimed to exploit the inhibition of PI3K in this context. In animal models of asthma, selective δ and γ inhibitors have shown to be effective, and when administered by inhalation, reasonably safe. Nevertheless, very few clinical trials have been performed so far. The efficacy of current traditional therapies for allergic bronchial asthma has likely diminished the need for new alternative treatments. Surprisingly, in COPD, where instead there is an urgent need for new and more effective therapeutic approaches, the number of clinical studies is still low and not capable yet, with the exception for an acceptable safety profile, to show a significant improvement of clinical outcomes. In IPF, a disease with a disappointing prognosis, PI3K inhibitors have been bound to a FAP ligand with the aim to selectively target myofibroblasts, showing to significantly reduce collagen production and the development of lung fibrosis in an animal model of lung fibrosis. Due to its role in cell activation and cell replication, the PI3K pathway is obviously largely involved in lung cancer. Several studies, currently ongoing, are testing the effect of PI3K inhibitors mainly in NSCLC. Some evidence in the treatment of cancer patients suggests the possibility that PI3K inhibitors may enhance the response to conventional treatment. The involvement of PI3Kδ in the modulation of airway neutrophil recruitment and bronchial epithelial functional alterations also suggest a potential role in the treatment of ARDS, but at the current state the ongoing trials are aimed to the treatment of ARDS in COVID-19 patients. In general, few clinical trials investigating PI3K inhibitors in respiratory disorders have been performed so far. This relatively new approach of treatment is just at its beginning and certainly needs further efforts and additional studies.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":"437-466"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33512485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Virology of Chikungunya Virus.","authors":"I Frolov,&nbsp;E I Frolova","doi":"10.1007/82_2018_146","DOIUrl":"https://doi.org/10.1007/82_2018_146","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) was discovered more than six decades ago, but has remained poorly investigated. However, after a recent outbreak of CHIK fever in both hemispheres and viral adaptation to new species of mosquitoes, it has attracted a lot of attention. The currently available experimental data suggest that molecular mechanisms of CHIKV replication in vertebrate and mosquito cells are similar to those of other New and Old World alphaviruses. However, this virus exhibits a number of unique characteristics that distinguish it from the other, better studied members of the alphavirus genus. This review is an attempt to summarize the data accumulated thus far regarding the molecular mechanisms of alphavirus RNA replication and interaction with host cells. Emphasis was placed on demonstrating the distinct features of CHIKV in utilizing host factors to build replication complexes and modify the intracellular environment for efficient viral replication and inhibition of the innate immune response. The available data suggest that our knowledge about alphavirus replication contains numerous gaps that potentially hamper the development of new therapeutic means against CHIKV and other pathogenic alphaviruses.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":"1-31"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/82_2018_146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36814919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PI3K Isoforms in CD8⁺ T Cell Development and Function.","authors":"Pankaj Gaur,&nbsp;Mikayel Mkrtichyan,&nbsp;Vivek Verma,&nbsp;Nazli Jafarzadeh,&nbsp;Mariana Hattar,&nbsp;Seema Gupta,&nbsp;Samir N Khleif","doi":"10.1007/978-3-031-06566-8_9","DOIUrl":"https://doi.org/10.1007/978-3-031-06566-8_9","url":null,"abstract":"<p><p>CD8⁺ T cells are an essential part of the immune system and play a vital role in defending against tumors and infections. The phosphoinositide-3-kinase (PI3K), especially class I, is involved in numerous interrelated signaling pathways which control CD8⁺ T cell development, maturation, migration, activation, and differentiation. While CD8⁺ T lymphocytes express all class I PI3K isoforms (PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ), isoform-specific functions, especially for PI3Kα and PI3Kβ have not been fully elucidated. A few studies suggest the important role of p110δ and p110γ in CD8⁺ T cell activation, signaling, chemotaxis and function and several clinical trials are currently testing the effect of isoform-specific inhibitors in various types of cancers, including Indolent Non-Hodgkin Lymphoma, Peripheral T cell Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, non-small cell lung carcinoma (NSCLC), head & neck cancer, and breast cancer. This chapter summarizes current knowledge of the roles of various PI3K isoforms and downstream signaling pathways in regulating CD8⁺ T cell fate, including cell proliferation, migration, and memory generation. We also discuss certain clinical trials employing PI3K inhibitors for cancer therapy, their limitations, and future perspectives.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":"217-234"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33514448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-amplifying mRNA-Based Vaccine Technology and Its Mode of Action.","authors":"Giulietta Maruggi,&nbsp;Jeffrey B Ulmer,&nbsp;Rino Rappuoli,&nbsp;Dong Yu","doi":"10.1007/82_2021_233","DOIUrl":"https://doi.org/10.1007/82_2021_233","url":null,"abstract":"<p><p>Self-amplifying mRNAs derived from the genomes of positive-strand RNA viruses have recently come into focus as a promising technology platform for vaccine development. Non-virally delivered self-amplifying mRNA vaccines have the potential to be highly versatile, potent, streamlined, scalable, and inexpensive. By amplifying their genome and the antigen encoding mRNA in the host cell, the self-amplifying mRNA mimics a viral infection, resulting in sustained levels of the target protein combined with self-adjuvanting innate immune responses, ultimately leading to potent and long-lasting antigen-specific humoral and cellular immune responses. Moreover, in principle, any eukaryotic sequence could be encoded by self-amplifying mRNA without the need to change the manufacturing process, thereby enabling a much faster and flexible research and development timeline than the current vaccines and hence a quicker response to emerging infectious diseases. This chapter highlights the rapid progress made in using non-virally delivered self-amplifying mRNA-based vaccines against infectious diseases in animal models. We provide an overview of the unique attributes of this vaccine approach, summarize the growing body of work defining its mechanism of action, discuss the current challenges and latest advances, and highlight perspectives about the future of this promising technology.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":"440 ","pages":"31-70"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/82_2021_233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9113422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Molecule Inhibitors Targeting Chikungunya Virus.","authors":"Nicole Haese,&nbsp;John Powers,&nbsp;Daniel N Streblow","doi":"10.1007/82_2020_195","DOIUrl":"https://doi.org/10.1007/82_2020_195","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) infection in humans is rarely fatal but is often associated with chronic joint and muscle pain. Chronic CHIKV disease is highly debilitating and is associated with viral persistence. To date, there are no approved vaccines or therapeutics to prevent or treat CHIKV infections once they are established. Current palliative treatments aim to reduce joint inflammation and pain associated with acute and chronic CHIKV disease. Development of novel therapeutics that reduces viral loads should positively impact virus inflammatory disease and improve patient outcomes following CHIKV infection. Therapies that target multiple aspects of CHIKV replication cycle should be developed since the virus is capable of rapidly mutating around any single therapeutic. This review summarizes the current status of small molecule inhibitor development against CHIKV.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":"435 ","pages":"107-139"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/82_2020_195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10398491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Chikungunya Virus Disease.","authors":"Mary K McCarthy,&nbsp;Bennett J J Davenport,&nbsp;Thomas E Morrison","doi":"10.1007/82_2018_147","DOIUrl":"https://doi.org/10.1007/82_2018_147","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has caused both small- and large-scale epidemics of incapacitating musculoskeletal disease across the globe. A substantial proportion of infected individuals experience debilitating arthralgia and/or arthritis that can persist in relapsing or continuous forms for months to years, an occurrence that appears independent of viral strain and outbreak location. Due to the lack of CHIKV-specific vaccine or therapeutics, treatment of chronic CHIKV disease is limited to supportive care. Although the epidemiologic and molecular mechanisms that dictate resolution or chronicity of CHIKV disease remain unclear, several risk factors and immunological responses have been implicated in the development of chronic CHIKV disease. Mounting evidence from animal models and limited case studies indicates that chronic disease is likely a result of induced autoimmunity and/or viral persistence in joint-associated tissue. Due to the global spread and explosive, often unpredictable nature of CHIKV epidemics, concerted efforts to obtain a more precise understanding of the development and maintenance of chronic CHIKV disease must be at the forefront of investigative endeavors.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":"435 ","pages":"55-80"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/82_2018_147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10755550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}