The Role of Cell-specific Tropism in the Pathogenesis of Rhesus Cytomegalovirus Infection

The Role of Cell-specific Tropism in the Pathogenesis of Rhesus Cytomegalovirus Infection PDF Author: Basel Tareq Assaf
Publisher:
ISBN: 9781267758330
Category :
Languages : en
Pages :

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Book Description
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.

Human Herpesviruses

Human Herpesviruses PDF Author: Ann Arvin
Publisher: Cambridge University Press
ISBN: 1139461648
Category : Medical
Languages : en
Pages : 1325

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Book Description
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

Human Cytomegalovirus PDF Author: Thomas E. Shenk
Publisher: Springer Science & Business Media
ISBN: 3540773495
Category : Medical
Languages : en
Pages : 477

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Book Description
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.

Chimpanzees in Biomedical and Behavioral Research

Chimpanzees in Biomedical and Behavioral Research PDF Author: National Research Council
Publisher: National Academies Press
ISBN: 0309220424
Category : Science
Languages : en
Pages : 200

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Book Description
For many years, experiments using chimpanzees have been instrumental in advancing scientific knowledge and have led to new medicines to prevent life-threatening and debilitating diseases. However, recent advances in alternate research tools have rendered chimpanzees largely unnecessary as research subjects. The Institute of Medicine, in collaboration with the National Research Council, conducted an in-depth analysis of the scientific necessity for chimpanzees in NIH-funded biomedical and behavioral research. The committee concludes that while the chimpanzee has been a valuable animal model in the past, most current biomedical research use of chimpanzees is not necessary, though noted that it is impossible to predict whether research on emerging or new diseases may necessitate chimpanzees in the future.

Persistent Viral Infections

Persistent Viral Infections PDF Author: R. Ahmed
Publisher: Wiley-Blackwell
ISBN:
Category : Medical
Languages : en
Pages : 754

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Book Description
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.

The Human Herpesviruses

The Human Herpesviruses PDF Author: Bernard Roizman
Publisher: Raven Press (ID)
ISBN:
Category : Medical
Languages : en
Pages : 458

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Book Description


Fields Virology: Emerging Viruses

Fields Virology: Emerging Viruses PDF Author: Peter M. Howley
Publisher: Lippincott Williams & Wilkins
ISBN: 1975112555
Category : Medical
Languages : en
Pages : 2597

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Book Description
Now in four convenient volumes, Field’s Virology remains the most authoritative reference in this fast-changing field, providing definitive coverage of virology, including virus biology as well as replication and medical aspects of specific virus families. This volume of Field’s Virology: Emerging Viruses, 7th Edition covers recent changes in emerging viruses, providing new or extensively revised chapters that reflect these advances in this dynamic field.

Essential Human Virology

Essential Human Virology PDF Author: Jennifer Louten
Publisher: Academic Press
ISBN: 0323914926
Category : Science
Languages : en
Pages : 412

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Book Description
Essential Human Virology, Second Edition focuses on the structure and classification of viruses, virus transmission and virus replication strategies based upon type of viral nucleic acid. Several chapters focus on notable and recognizable viruses and the diseases caused by them, including influenza, HIV, hepatitis viruses, poliovirus, herpesviruses and emerging and dangerous viruses. Additionally, how viruses cause disease (pathogenesis) is highlighted, along with discussions on immune response to viruses, vaccines, anti-viral drugs, gene therapy, the beneficial uses of viruses, research laboratory assays and viral diagnosis assays. Fully revised and updated with new chapters on coronaviruses, nonliving infectious agents, and notable non-human viruses, the book provides students with a solid foundation in virology. Focuses on human diseases and the cellular pathology that viruses cause Highlights current and cutting-edge technology and associated issues Presents real case studies and current news highlights in each chapter Features dynamic illustrations, chapter assessment questions, key terms, and a summary of concepts, as well as an instructor website with lecture slides, a test bank and recommended activities Updated and revised, with new chapters on coronaviruses, nonliving infectious agents, and notable non-human viruses

Epstein Barr Virus Volume 1

Epstein Barr Virus Volume 1 PDF Author: Christian Münz
Publisher: Springer
ISBN: 9783319228211
Category : Medical
Languages : en
Pages : 0

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Book Description
Epstein Barr virus (EBV) was discovered as the first human tumor virus around 50 years ago. Since its discovery in Burkitt’s lymphoma it has been associated with various other malignancies, infectious mononucleosis and even autoimmune diseases. The two book volumes on EBV summarize the first 50 years of research on this tumor virus, starting with historical perspectives on discovery, oncogenicity and immune control, reviewing the role that the virus plays in the various associated diseases and concluding with a discussion on how the immune system keeps persistent EBV infection under control in healthy EBV carriers and can be used to treat EBV associated diseases. The respective 32 chapters are written by international experts from three continents for health care providers, biomedical researchers and patients that are affected by EBV. The assembled knowledge should help to understand EBV associated diseases better and to develop EBV specific vaccination in the near future.

Vaccines for the 21st Century

Vaccines for the 21st Century PDF Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309174988
Category : Medical
Languages : en
Pages : 472

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Book Description
Vaccines have made it possible to eradicate the scourge of smallpox, promise the same for polio, and have profoundly reduced the threat posed by other diseases such as whooping cough, measles, and meningitis. What is next? There are many pathogens, autoimmune diseases, and cancers that may be promising targets for vaccine research and development. This volume provides an analytic framework and quantitative model for evaluating disease conditions that can be applied by those setting priorities for vaccine development over the coming decades. The committee describes an approach for comparing potential new vaccines based on their impact on morbidity and mortality and on the costs of both health care and vaccine development. The book examines: Lessons to be learned from the polio experience. Scientific advances that set the stage for new vaccines. Factors that affect how vaccines are used in the population. Value judgments and ethical questions raised by comparison of health needs and benefits. The committee provides a way to compare different forms of illness and set vaccine priorities without assigning a monetary value to lives. Their recommendations will be important to anyone involved in science policy and public health planning: policymakers, regulators, health care providers, vaccine manufacturers, and researchers.