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Book Synopsis Cytomegalovirus Pathogenesis and Host Interactions by : Emma Poole
Download or read book Cytomegalovirus Pathogenesis and Host Interactions written by Emma Poole and published by Frontiers Media SA. This book was released on 2021-04-21 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt:
This volume has gathered some of the experts in the field to review aspects of our understanding of CMV and to offer perspectives of the current problems associated with CMV. The editors and authors hope that the chapters will lead to a better understanding of the virus that will assist in the development of new and unique antivirals, a protective vaccine, and a full understanding of CMV's involvement in human disease.
Book Synopsis Human Cytomegalovirus by : Thomas E. Shenk
Download or read book Human Cytomegalovirus written by Thomas E. Shenk and published by Springer Science & Business Media. This book was released on 2008-05-09 with total page 477 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume has gathered some of the experts in the field to review aspects of our understanding of CMV and to offer perspectives of the current problems associated with CMV. The editors and authors hope that the chapters will lead to a better understanding of the virus that will assist in the development of new and unique antivirals, a protective vaccine, and a full understanding of CMV's involvement in human disease.
Human Cytomegalovirus (CMV) - a member of the herpesvirus family - is an underrated health risk. A low public awareness results from the relatively mild symptoms it causes in otherwise healthy people whose immune systems are intact, with primary infection usually going unnoticed. During pregnancy, however, transmission from the mother to the fetus is currently the most frequent viral cause of birth defects with lifelong neurological sequelae, sensorineural hearing loss in particular. People at risk also include the growing number of immune compromised patients requiring either a solid organ graft or receiving a hematopoietic cell graft for the treatment of hematopoietic malignancies that are refractory to standard therapies. Under the condition of weakened immune surveillance in these patients, latent CMV hidden in transplanted donor cells or in the recipients' own tissues can awake to cause a destructive infection resulting in graft loss and multiple end-organ disease, of which viral pneumonia is the most feared. This two volume work is an updated and upgraded second edition of Cytomegaloviruses: Molecular Biology and Immunology (2006). The second edition's title - Cytomegaloviruses: From Molecular Pathogenesis to Intervention - reflects its expanded commitment not only to cover cutting edge basic science, but also to include the translation of this to clinical science. In an interdisciplinary approach to understanding CMV disease and outlining options for prevention and treatment, leading international experts provide comprehensive and authoritative reviews on literally every aspect of current research with an unprecedented completeness, integrating research on human CMV and insights gained from experimental animal models. With contributions from over 100 authors, the topics covered in the 46 chapters range from the most contemporary systems biology 'omics' views on virus-host interaction to considerations of the health and economic impact of CMV disease for evaluating the hoped-for benefit from a vaccine. Volume 1 (as an individual volume: ISBN 978 1 908230 19 5) focuses on basic science laying the foundations of clinical research, starting with the comparative genomics of primate CMVs and ending with the emerging field of humanized mouse models. This Volume 2 (as an individual volume: ISBN 978 1 908230 20 1; as a two volume set: ISBN 978 1 908230 18 8) is more clinically oriented, covering the immune response to CMV, the most pressing medical problems in the newborn and in transplantation patients, as well as diagnostics, the management of antiviral drug resistance, the state and future of a CMV vaccine, and the potential of using CMV as a vaccine vector to fight unrelated diseases. The book closes with a critical survey of disputed associations between CMV and atherosclerotic cardiovascular disease, certain tumors such as Glioblastoma Multiforme, and the phenomenon of 'immune senescence' in the elderly. The two volume set (ISBN 978 1 908230 18 8) is liberally illustrated with more than 200 figures, most of which are in full color. There are over 60 tables and several thousand references which enhance the set even further, making it an invaluable source of information. This will be essential reading for all virologists with an interest in cytomegaloviruses, for all clinicians in pediatric intensive care medicine and at transplantation centers, for scientists working on antiviral drug and vaccine development, as well as for public health service and science funding system authorities.
Book Synopsis Cytomegaloviruses by : Matthias Johannes Reddehase
Download or read book Cytomegaloviruses written by Matthias Johannes Reddehase and published by Caister Academic Press Limited. This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human Cytomegalovirus (CMV) - a member of the herpesvirus family - is an underrated health risk. A low public awareness results from the relatively mild symptoms it causes in otherwise healthy people whose immune systems are intact, with primary infection usually going unnoticed. During pregnancy, however, transmission from the mother to the fetus is currently the most frequent viral cause of birth defects with lifelong neurological sequelae, sensorineural hearing loss in particular. People at risk also include the growing number of immune compromised patients requiring either a solid organ graft or receiving a hematopoietic cell graft for the treatment of hematopoietic malignancies that are refractory to standard therapies. Under the condition of weakened immune surveillance in these patients, latent CMV hidden in transplanted donor cells or in the recipients' own tissues can awake to cause a destructive infection resulting in graft loss and multiple end-organ disease, of which viral pneumonia is the most feared. This two volume work is an updated and upgraded second edition of Cytomegaloviruses: Molecular Biology and Immunology (2006). The second edition's title - Cytomegaloviruses: From Molecular Pathogenesis to Intervention - reflects its expanded commitment not only to cover cutting edge basic science, but also to include the translation of this to clinical science. In an interdisciplinary approach to understanding CMV disease and outlining options for prevention and treatment, leading international experts provide comprehensive and authoritative reviews on literally every aspect of current research with an unprecedented completeness, integrating research on human CMV and insights gained from experimental animal models. With contributions from over 100 authors, the topics covered in the 46 chapters range from the most contemporary systems biology 'omics' views on virus-host interaction to considerations of the health and economic impact of CMV disease for evaluating the hoped-for benefit from a vaccine. Volume 1 (as an individual volume: ISBN 978 1 908230 19 5) focuses on basic science laying the foundations of clinical research, starting with the comparative genomics of primate CMVs and ending with the emerging field of humanized mouse models. This Volume 2 (as an individual volume: ISBN 978 1 908230 20 1; as a two volume set: ISBN 978 1 908230 18 8) is more clinically oriented, covering the immune response to CMV, the most pressing medical problems in the newborn and in transplantation patients, as well as diagnostics, the management of antiviral drug resistance, the state and future of a CMV vaccine, and the potential of using CMV as a vaccine vector to fight unrelated diseases. The book closes with a critical survey of disputed associations between CMV and atherosclerotic cardiovascular disease, certain tumors such as Glioblastoma Multiforme, and the phenomenon of 'immune senescence' in the elderly. The two volume set (ISBN 978 1 908230 18 8) is liberally illustrated with more than 200 figures, most of which are in full color. There are over 60 tables and several thousand references which enhance the set even further, making it an invaluable source of information. This will be essential reading for all virologists with an interest in cytomegaloviruses, for all clinicians in pediatric intensive care medicine and at transplantation centers, for scientists working on antiviral drug and vaccine development, as well as for public health service and science funding system authorities.
This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.
Book Synopsis Human Herpesviruses by : Ann Arvin
Download or read book Human Herpesviruses written by Ann Arvin and published by Cambridge University Press. This book was released on 2007-08-16 with total page 1325 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.
Human cytomegalovirus (HCMV), a beta-herpesvirus, is an important opportunistic pathogen that primarily affects individuals with compromised or immature immune systems. It is of great significance in AIDS patients where it can cause serious morbidity through retinitis-associated blindness, and other complications, such as pneumonia and enteritis. In developed nations, it is a leading viral cause of congenital disease, where in-utero infection manifests in mental and behavioral disorders. In order to control infection and HCMV associated disease, new compounds and novel strategies must be developed. Understanding the role viral proteins play during the course of infection will help elucidate the mechanisms of HCMV pathogenesis and provide important information on potential targets for new treatments. However, the strict species specificity of HCMV prevents any studies into the pathogenesis of the virus in an animal host. This limitation can be overcome through the use of murine cytomegalovirus (MCMV). MCMV, like HCMV, is a betaherpesvirus that exhibits similar pathogenesis in mice to HCMV infection in the human host. The genetic structure of MCMV contains significant sequence homology to HCMV AD169 in at least 78 ORFs and can thereby be used as an important tool in elucidating the functions of these ORFs in a complete in vivo system. In our study, we have conducted a comprehensive YTH screen to identify potential interactions between approximately 170 MCMV ORFs. Growth phenotype analysis were also conducted using five different cell lines potentially involved in various aspects of CMV infection. Between these 170 predicted proteins we have identified 94 potential interactions that exhibit varying levels of essentiality depending on the type of cell infected. We aim to understand the nature of the interactions between the viral particle and proteins encoded by the virus in order to elucidate potential mechanisms by which these proteins help to assemble and create new progeny viruses. The interactions that we have identified in this study provide a framework to predict the functions of uncharacterized viral proteins. And understanding the importance of each protein in the context of infection can further help to determine the nature of these unknown viral proteins. Together using information about known viral proteins that interact with these unknown elements, we can develop a better understanding of how all of these components contribute to viral infection which can be used to determine more effective methods to treat or prevent CMV associated diseases.
Book Synopsis Global Analysis of Murine Cytomegalovirus Open Reading Frames Using Yeast Two-Hybrid and Growth Phenotype Analysis by : Sean Umamoto
Download or read book Global Analysis of Murine Cytomegalovirus Open Reading Frames Using Yeast Two-Hybrid and Growth Phenotype Analysis written by Sean Umamoto and published by . This book was released on 2011 with total page 264 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human cytomegalovirus (HCMV), a beta-herpesvirus, is an important opportunistic pathogen that primarily affects individuals with compromised or immature immune systems. It is of great significance in AIDS patients where it can cause serious morbidity through retinitis-associated blindness, and other complications, such as pneumonia and enteritis. In developed nations, it is a leading viral cause of congenital disease, where in-utero infection manifests in mental and behavioral disorders. In order to control infection and HCMV associated disease, new compounds and novel strategies must be developed. Understanding the role viral proteins play during the course of infection will help elucidate the mechanisms of HCMV pathogenesis and provide important information on potential targets for new treatments. However, the strict species specificity of HCMV prevents any studies into the pathogenesis of the virus in an animal host. This limitation can be overcome through the use of murine cytomegalovirus (MCMV). MCMV, like HCMV, is a betaherpesvirus that exhibits similar pathogenesis in mice to HCMV infection in the human host. The genetic structure of MCMV contains significant sequence homology to HCMV AD169 in at least 78 ORFs and can thereby be used as an important tool in elucidating the functions of these ORFs in a complete in vivo system. In our study, we have conducted a comprehensive YTH screen to identify potential interactions between approximately 170 MCMV ORFs. Growth phenotype analysis were also conducted using five different cell lines potentially involved in various aspects of CMV infection. Between these 170 predicted proteins we have identified 94 potential interactions that exhibit varying levels of essentiality depending on the type of cell infected. We aim to understand the nature of the interactions between the viral particle and proteins encoded by the virus in order to elucidate potential mechanisms by which these proteins help to assemble and create new progeny viruses. The interactions that we have identified in this study provide a framework to predict the functions of uncharacterized viral proteins. And understanding the importance of each protein in the context of infection can further help to determine the nature of these unknown viral proteins. Together using information about known viral proteins that interact with these unknown elements, we can develop a better understanding of how all of these components contribute to viral infection which can be used to determine more effective methods to treat or prevent CMV associated diseases.
Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.
Book Synopsis Persistent Viral Infections by : R. Ahmed
Download or read book Persistent Viral Infections written by R. Ahmed and published by Wiley-Blackwell. This book was released on 1999 with total page 754 pages. Available in PDF, EPUB and Kindle. Book excerpt: Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.
Here is the most complete reference devoted specifically to viral pathogenesis, describing both the development of viral disease and the host/virus interaction. Presenting contributions from leading authorities in this particularly topical field, this comprehensive text exposits the current knowledge on the pathogenesis of viruses, an understanding of which is critical to treatment and prevention of viral diseases. The book opens with a thorough review of principles, covering in detail the life cycle of viruses, including entry, dissemination, shedding and transmission, and replication; the pathology of viral disease, including disease mechanisms, virus virulence, and viral oncogenesis; immune responses, including immune suppression; and therapeutic applications. The second section focuses on experimental pathogenesis, covering detection and quantification of viral genomes, messages, and proteins in tissues and organs; and examining classical and new methods for animal studies. Chapters in the next section, devoted to classical models of viral pathogenesis, cover ectromelia, poliomyelitis, rabies, lymphocytic choriomeningitis virus, avian and murine retroviruses, lentiviruses, and reoviruses. The final section covers systems pathogenesis, emphasizing viral diseases of humans but also drawing on animal studies that elucidate the pathogenesis of human infections.
Book Synopsis Viral Pathogenesis by : Neal Nathanson
Download or read book Viral Pathogenesis written by Neal Nathanson and published by Lippincott Williams & Wilkins. This book was released on 1997 with total page 970 pages. Available in PDF, EPUB and Kindle. Book excerpt: Here is the most complete reference devoted specifically to viral pathogenesis, describing both the development of viral disease and the host/virus interaction. Presenting contributions from leading authorities in this particularly topical field, this comprehensive text exposits the current knowledge on the pathogenesis of viruses, an understanding of which is critical to treatment and prevention of viral diseases. The book opens with a thorough review of principles, covering in detail the life cycle of viruses, including entry, dissemination, shedding and transmission, and replication; the pathology of viral disease, including disease mechanisms, virus virulence, and viral oncogenesis; immune responses, including immune suppression; and therapeutic applications. The second section focuses on experimental pathogenesis, covering detection and quantification of viral genomes, messages, and proteins in tissues and organs; and examining classical and new methods for animal studies. Chapters in the next section, devoted to classical models of viral pathogenesis, cover ectromelia, poliomyelitis, rabies, lymphocytic choriomeningitis virus, avian and murine retroviruses, lentiviruses, and reoviruses. The final section covers systems pathogenesis, emphasizing viral diseases of humans but also drawing on animal studies that elucidate the pathogenesis of human infections.
The 40-year quest for a vaccine against human cytomegalovirus (HCMV) infection has been partially met by targeting the major envelope glycoprotein B (gB). However, the complex natural history of HCMV and the virus ability to infect a wide range of host cell types illustrate the central role cellular tropism plays in HCMV pathogenesis and emphasize the need for a vaccine that targets additional viral determinants of cellular tropism. Multiple genes located within the UL/b' region (UL128-UL154) of the HCMV genome have been implicated in regulating virus entry into epithelial and endothelial cells and modulating several host immune responses mounted against HCMV infection. We utilized virological, histopathological, and epidemiological tools to characterize the relationship between rhesus cytomegalovirus (RhCMV) cellular tropism and the pattern of viral infection in vivo and illustrated the potential of targeting products of genes within the UL/b' region in future vaccine developments. To address this, we inoculated rhesus macaques with three RhCMV strains that vary in their UL/b' coding content. RhCMV UCD52 and UCD59 encode a full complement of open reading frames (ORF) in the UL/b' region; RhCMV 68-1 lacks the UL128 complex essential for endothelial/epithelial tropism, and alpha-chemokine-like ORFs; and RhCMV 180.92 tropic for endothelial/epithelial cells but lacks viral determinants of host immune evasion.Two histopathological hallmarks were observed with the acute infection with RhCMV UCD52 and UCD59 strains: neutrophilic inflammation and infected endothelial cells, both of which were observed during recurrent RhCMV disease in animals coinfected with wild-type RhCMV and simian immunodeficiency virus (SIV). In contrast, animals inoculated with RhCMV 68-1 were noted for an absence of neutrophilic infiltrates and infected endothelial cells, demonstrating the role of UL128 complex in epithelial/endothelial tropism in vivo and further suggest that the long-term pattern of viral infection is determined in large part by the earliest virus-host interactions. Further investigations using RhCMV 180.92 demonstrated lower levels of plasma viremia, limited systemic dissemination, low levels of tissue virus titers, and absent or low level of viral shedding in urine and saliva, compared to the in vivo pattern of a minor RhCMV 180.92 variant present in the virus stock potentially carrying the full complement of UL/b' region. These results demonstrate the possibility that other ORFs, independent of UL128 complex, within the UL/b' region may determine in vivo viral replication, dissemination, and shedding of RhCMV.Finally, RhCMV neuromuscular disease was identified in 10.5% of all SIV-infected animals and 6% demonstrated direct RhCMV infection of skeletal muscles. HCMV has been implicated by association in the pathogenesis of HIV-associated myopathies. However, in vivo studies failed to demonstrate a direct evidence of HCMV infection of skeletal muscle cells. Our results indicate that RhCMV is linked to skeletal myositis and suggest that human HCMV may be a causative agent for similar pathologies in HIV-infected humans.
Book Synopsis The Role of Cell-specific Tropism in the Pathogenesis of Rhesus Cytomegalovirus Infection by : Basel Tareq Assaf
Download or read book The Role of Cell-specific Tropism in the Pathogenesis of Rhesus Cytomegalovirus Infection written by Basel Tareq Assaf and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The 40-year quest for a vaccine against human cytomegalovirus (HCMV) infection has been partially met by targeting the major envelope glycoprotein B (gB). However, the complex natural history of HCMV and the virus ability to infect a wide range of host cell types illustrate the central role cellular tropism plays in HCMV pathogenesis and emphasize the need for a vaccine that targets additional viral determinants of cellular tropism. Multiple genes located within the UL/b' region (UL128-UL154) of the HCMV genome have been implicated in regulating virus entry into epithelial and endothelial cells and modulating several host immune responses mounted against HCMV infection. We utilized virological, histopathological, and epidemiological tools to characterize the relationship between rhesus cytomegalovirus (RhCMV) cellular tropism and the pattern of viral infection in vivo and illustrated the potential of targeting products of genes within the UL/b' region in future vaccine developments. To address this, we inoculated rhesus macaques with three RhCMV strains that vary in their UL/b' coding content. RhCMV UCD52 and UCD59 encode a full complement of open reading frames (ORF) in the UL/b' region; RhCMV 68-1 lacks the UL128 complex essential for endothelial/epithelial tropism, and alpha-chemokine-like ORFs; and RhCMV 180.92 tropic for endothelial/epithelial cells but lacks viral determinants of host immune evasion.Two histopathological hallmarks were observed with the acute infection with RhCMV UCD52 and UCD59 strains: neutrophilic inflammation and infected endothelial cells, both of which were observed during recurrent RhCMV disease in animals coinfected with wild-type RhCMV and simian immunodeficiency virus (SIV). In contrast, animals inoculated with RhCMV 68-1 were noted for an absence of neutrophilic infiltrates and infected endothelial cells, demonstrating the role of UL128 complex in epithelial/endothelial tropism in vivo and further suggest that the long-term pattern of viral infection is determined in large part by the earliest virus-host interactions. Further investigations using RhCMV 180.92 demonstrated lower levels of plasma viremia, limited systemic dissemination, low levels of tissue virus titers, and absent or low level of viral shedding in urine and saliva, compared to the in vivo pattern of a minor RhCMV 180.92 variant present in the virus stock potentially carrying the full complement of UL/b' region. These results demonstrate the possibility that other ORFs, independent of UL128 complex, within the UL/b' region may determine in vivo viral replication, dissemination, and shedding of RhCMV.Finally, RhCMV neuromuscular disease was identified in 10.5% of all SIV-infected animals and 6% demonstrated direct RhCMV infection of skeletal muscles. HCMV has been implicated by association in the pathogenesis of HIV-associated myopathies. However, in vivo studies failed to demonstrate a direct evidence of HCMV infection of skeletal muscle cells. Our results indicate that RhCMV is linked to skeletal myositis and suggest that human HCMV may be a causative agent for similar pathologies in HIV-infected humans.
This book highlights information derived primarily from clinical samples, with particular reference to theoretical and scientific aspects of the human immune system. This text will focus on topics that range from host-pathogen interactions in infectious disease to host immune response in cancer, allergic diseases, neuroinflammatory diseases, and autoimmune disorders. The reader will also have a well-rounded understanding of the behavior of the immune system with particular emphasis on the role of immunoproteomics in immunotherapy, neuroprotective immunity for neurodegenerative and neuroinfectious disease, leukemia-associated dendritic cell induction of adaptive immunity dysregulation, and the role of immune checkpoint inhibitors in cancer, infection, as well as neuroinflammation. Taken together, the contents of this book are intended for both clinicians and researchers in academia and industry.
Book Synopsis Advanced Concepts in Human Immunology: Prospects for Disease Control by : Pooja Jain
Download or read book Advanced Concepts in Human Immunology: Prospects for Disease Control written by Pooja Jain and published by Springer Nature. This book was released on 2020-08-11 with total page 413 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book highlights information derived primarily from clinical samples, with particular reference to theoretical and scientific aspects of the human immune system. This text will focus on topics that range from host-pathogen interactions in infectious disease to host immune response in cancer, allergic diseases, neuroinflammatory diseases, and autoimmune disorders. The reader will also have a well-rounded understanding of the behavior of the immune system with particular emphasis on the role of immunoproteomics in immunotherapy, neuroprotective immunity for neurodegenerative and neuroinfectious disease, leukemia-associated dendritic cell induction of adaptive immunity dysregulation, and the role of immune checkpoint inhibitors in cancer, infection, as well as neuroinflammation. Taken together, the contents of this book are intended for both clinicians and researchers in academia and industry.
Human cytomegalovirus (HCMV) infection in newborns and immunocompromised individuals with immature or deficient immune systems can cause life-threatening diseases. The clinical and subsequent economical burden of HCMV infection led the US Institute of Medicine designating a vaccine for HCMV as the highest level of priority. Complex virus-host interactions have developed over millions of years of co-evolution, making the understanding of the pathogenesis of HCMV disease particularly challenging. Consequently, a crucial factor in aiding the development of effective vaccinations and therapies to significantly reduce morbidity and mortality associated with HCMV infection is elucidating what immune mechanisms contribute to/impede protection against infection. For example, is the induction of immunomodulatory agents such as cytokines beneficial or harmful to the host during infection? Given the known immunosuppressive properties of one such cytokine, interleukin-10 (IL-10), in conjunction with the evolutionary acquisition by HCMV of its own IL-10 homologue, I hypothesised that mammalian- and viral-IL-10 suppress protective immunity during acute CMV infection. Utilising a mouse model of CMV infection, I revealed a surprising antiviral role for IL-10 during acute infection in vivo, which was achieved via limitation of activation-induced death of NK cells. The IL-10-related cytokine interleukin-22 (IL-22) provides critical protection against certain infectious agents and I therefore hypothesised that IL-22 provides protective immunity during acute CMV infection. Utilising the murine infection model once more, I discovered a tissue-specific antiviral role for IL-22 during acute infection in vivo and made the surprising finding that neutrophils play a protective role during infection. I also demonstrated that neutrophils can directly inhibit viral replication in vitro. Thus, novel insights into cytokine biology in the context of viral infections in vivo revealed by these studies highlighted important considerations for future research into herpesvirus infections, and has major implications for the treatment of this important infectious disease.
Book Synopsis Investigation of Mammalian and Viral Interleukin-10 Family Members During Cytomegalovirus Infection by : Maria A. Stacey
Download or read book Investigation of Mammalian and Viral Interleukin-10 Family Members During Cytomegalovirus Infection written by Maria A. Stacey and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Human cytomegalovirus (HCMV) infection in newborns and immunocompromised individuals with immature or deficient immune systems can cause life-threatening diseases. The clinical and subsequent economical burden of HCMV infection led the US Institute of Medicine designating a vaccine for HCMV as the highest level of priority. Complex virus-host interactions have developed over millions of years of co-evolution, making the understanding of the pathogenesis of HCMV disease particularly challenging. Consequently, a crucial factor in aiding the development of effective vaccinations and therapies to significantly reduce morbidity and mortality associated with HCMV infection is elucidating what immune mechanisms contribute to/impede protection against infection. For example, is the induction of immunomodulatory agents such as cytokines beneficial or harmful to the host during infection? Given the known immunosuppressive properties of one such cytokine, interleukin-10 (IL-10), in conjunction with the evolutionary acquisition by HCMV of its own IL-10 homologue, I hypothesised that mammalian- and viral-IL-10 suppress protective immunity during acute CMV infection. Utilising a mouse model of CMV infection, I revealed a surprising antiviral role for IL-10 during acute infection in vivo, which was achieved via limitation of activation-induced death of NK cells. The IL-10-related cytokine interleukin-22 (IL-22) provides critical protection against certain infectious agents and I therefore hypothesised that IL-22 provides protective immunity during acute CMV infection. Utilising the murine infection model once more, I discovered a tissue-specific antiviral role for IL-22 during acute infection in vivo and made the surprising finding that neutrophils play a protective role during infection. I also demonstrated that neutrophils can directly inhibit viral replication in vitro. Thus, novel insights into cytokine biology in the context of viral infections in vivo revealed by these studies highlighted important considerations for future research into herpesvirus infections, and has major implications for the treatment of this important infectious disease.