More people were killed by smallpox during the twentieth century-over 300 million-than by all of the wars of that period combined. In 1918 and 1919, influenza virus claimed over 50 million lives. A century later, influenza is poised to return, ongoing plagues of HIV/AIDS and hepatitis infect millions, and Ebola, Zika, and West Nile viruses cause new concern and panic. The overlapping histories of humans and viruses are ancient. Earliest cities became both the cradle of civilization and breeding grounds for the first viral epidemics. This overlap is the focus of virologist/immunologist Michael Oldstone in Viruses, Plagues and History. Oldstone explains principles of viruses and epidemics while recounting stories of viruses and their impact on human history. This fully updated second edition includes engrossing new chapters on hepatitis, Zika, and contemporary threats such as the possible return of a catastrophic influenza, and the impact of fear of autism on vaccination efforts. This is a fascinating panorama of humankind's longstanding conflict with unseen viral enemies, both human successes-such as control of poliomyelitis, measles, smallpox and yellow fever, and continued dangers-such as HIV and Ebola. Impeccably researched and accessibly written, Viruses, Plagues and History will fascinate all with an interest in how viral illnesses alter the course of human history.

This volume focuses on the role of sphingosine-1-phosphate (S1P) and its analogs in the induced sequestration of lymphocytes in secondary lymphoid organs or in the microenvironment of tissues involved in infection or autoimmune disease. Initial chapters define the pathways to understand S1P signaling. They cover the organization of signaling systems, the structural biology of the S1P1 receptor, and the chemical and genetic tools that are available and useful to explore this area of research and therapeutics. The later chapters highlight S1P and endothelial integrity, lymphocyte migration in the spleen, and S1P agonist in controlling immunopathologic manifestations of acute respiratory influenza virus infection (in the lung), and its accompanying cytokine storm as well as immunopathologic disease of the central nervous system, including the beginning of treatments in multiple sclerosis. One chapter reveals the possible involvement of other lipid molecules, their use for better understanding lipid signaling, and their potential in the modulation of immune responses.

This two-volume work covers the molecular and cell biology, genetics and evolution of influenza viruses, the pathogenesis of infection, resultant host innate and adaptive immune response, prevention of infection through vaccination and approaches to the therapeutic control of infection.. Experts at the forefront of these areas provide critical assessments with regard to influenza virology, immunology, cell and molecular biology, and pathogenesis. Volume I provides overviews of the latest findings on molecular determinants of viral pathogenicity, virus entry and cell tropism, pandemic risk assessment, transmission and pathogenesis in animal species, viral evolution, ecology and antigenic variation, while Volume II focuses on the role of innate and adaptive immunity in pathogenesis, development of vaccines and antivirals.

The purpose of this review is to examine the potential role of molecular mimicry in the pathogenesis of human T-lymphotropic virus type 1 ((HTLV- 1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP)). Comp- hensive reviews on the pathogenic mechanisms of HTLV-1-associated human diseases are available throughout the medical literature (Bangham 2000,, 2003; Barmak et al. 2003; Jacobson 2002; Levin and Jacobson 1997; Nagai and Osame 2003; Osame 2002). Approximately 25 years ago the ?rst human retrovirus, HTLV-1, was isolated (Poeisz et al. 1980). Subsequently, infection with HTLV-1 was shown to cause adult T-cell leukemia (ATL) and HAM/TSP (Gessain et al. 1985; McFarlin and Blattner 1991; Osame et al. 1986; Poeisz et al. 1980; Yoshida et al. 1987). HTLV-1 may infect up to 30% of people in endemic areas and 10-20 million people worldwide (Barmak et al. 2003; Edlich et al. 2000). However, only 1%-5% develop either ATL or HAM/TSP, the remainder being clinically asymptomatic carriers of HTLV-1 (Bangham 2000, 2003; Barmak et al. 2003; Jacobson 2002; Levin and Jacobson 1997; Nagai and Osame 2003; Osame 2002). Why infection with HTLV-1 causes ATL or HAM/TSP in some people while the vast majority of individuals are asymptomatic is largely - known. Some possible factors that may differentiate the asymptomatic from the diseased state include viral strain, human histocompatibility leukocyte antigen (HLA), viral load, and the immune response (Bangham 2000, 2003; Barmak et al. 2003; Jacobson 2002; Levin and Jacobson 1997; Nagai and Osame 2003; Nagai et al. 1998; Niewiesk et al. 1994; Osame 2002).

This two-volume work covers the molecular and cell biology, genetics and evolution of influenza viruses, the pathogenesis of infection, resultant host innate and adaptive immune response, prevention of infection through vaccination and approaches to the therapeutic control of infection.. Experts at the forefront of these areas provide critical assessments with regard to influenza virology, immunology, cell and molecular biology, and pathogenesis. Volume I provides overviews of the latest findings on molecular determinants of viral pathogenicity, virus entry and cell tropism, pandemic risk assessment, transmission and pathogenesis in animal species, viral evolution, ecology and antigenic variation, while Volume II focuses on the role of innate and adaptive immunity in pathogenesis, development of vaccines and antivirals.

Measles virus, one of the most contagious of all human viruses, has been largely contained by the development and use of a vaccine that was introduced 50 years ago. These two volumes were timed to honor the introduction of the vaccine and to record the enormous advancements made in understanding the molecular and cell biology, pathogenesis, and control of this infectious disease. Where vaccine has been effectively delivered, endemic measles virus transmission has been eliminated. However, difficulties in vaccine delivery, lack of health care support and objection to vaccination in some communities continue to result in nearly 40 million cases and over 300,000 deaths per year from measles.

By itself measles virus infection has and still provides some of the most interesting phenomena in biology. Following infection of dendritic cells, measles virus causes a profound suppression of the host s immune response that lasts a number of months after apparent recovery from infection. Indeed, measles virus was the first virus to be associated with immunosuppression with many of the manifestations to be observed one hundred years later with HIV infection. Measles is also associated with development of both post-infectious encephalomyelitis, an autoimmune demyelinating disease, and subacute sclerosing panencephalitis, a slowly progressive neurodegenerative disorder. How measles virus infects cells, spreads to various tissues and causes disease, as well as the role of the immune response, generation of new vaccines, and use as a vector for gene delivery are topics covered in these two volumes. "

The second volume of Arenaviruses deals with the biology and the pathogenesis of arenaviruses primarily through the study of LCMV. Interestingly and appropriately, the fundamental observation of MHC restriction and CD8 cytotoxic T lymphocyte killing derived initially from studies with LCMV in the mouse has been expanded to studies of most human pathogens, viral, bacterial, parasitic, as well as events in cancer. The scope and importance of this observation was recognized by awarding the Nobel Prize in 1996 to Rolf Zinkernagel and Peter Doherty, long-time workers in the field of LCMV and arenavirus biology. Over the last 14 years many of the principles for understanding viral pathogenesis and biology of animal viruses have been defined, in great part from the lessons learned by studying LCMV. Those lessons and their implications are the subject of this second volume on the arenaviruses.

Microbes have evolved in an impressive and diverse range of strategies to subvert the host immune system. Two major types of strategies exist. The first is the evasion of recognition by the host, for example by using antigenic variation, masking of epitopes, the use of decoys, molecular mimicry, etc. The second is the modulation and/or suppression of the innate (e.g. complement, NK cells) and adaptive (e.g. antibodies) immune responses. A better understanding of the underlying mechanisms involved is critical for the rational design of novel therapeutic agents and vaccines to treat and/or prevent infectious diseases. Another area of active research is the application of microbial immunomodulatory factors in the treatment of human immunological disorders (e.g. inflammatory bowel disease and asthma) and as sources of pharmacologically active agents. In this book, internationally renown scientists critically review the current cutting-edge research in this area. Topics covered include the

This two-volume work covers the molecular and cell biology, genetics and evolution of influenza viruses, the pathogenesis of infection, resultant host innate and adaptive immune response, prevention of infection through vaccination and approaches to the therapeutic control of infection.. Experts at the forefront of these areas provide critical assessments with regard to influenza virology, immunology, cell and molecular biology, and pathogenesis. Volume I provides overviews of the latest findings on molecular determinants of viral pathogenicity, virus entry and cell tropism, pandemic risk assessment, transmission and pathogenesis in animal species, viral evolution, ecology and antigenic variation, while Volume II focuses on the role of innate and adaptive immunity in pathogenesis, development of vaccines and antivirals. 

This volume focuses on the role of sphingosine-1-phosphate (S1P) and its analogs in the induced sequestration of lymphocytes in secondary lymphoid organs or in the microenvironment of tissues involved in infection or autoimmune disease. Initial chapters define the pathways to understand S1P signaling. They cover the organization of signaling systems, the structural biology of the S1P1 receptor, and the chemical and genetic tools that are available and useful to explore this area of research and therapeutics. The later chapters highlight S1P and endothelial integrity, lymphocyte migration in the spleen, and S1P agonist in controlling immunopathologic manifestations of acute respiratory influenza virus infection (in the lung), and its accompanying cytokine storm as well as immunopathologic disease of the central nervous system, including the beginning of treatments in multiple sclerosis. One chapter reveals the possible involvement of other lipid molecules, their use for better understanding lipid signaling, and their potential in the modulation of immune responses.

This two-volume work covers the molecular and cell biology, genetics and evolution of influenza viruses, the pathogenesis of infection, resultant host innate and adaptive immune response, prevention of infection through vaccination and approaches to the therapeutic control of infection.. Experts at the forefront of these areas provide critical assessments with regard to influenza virology, immunology, cell and molecular biology, and pathogenesis. Volume I provides overviews of the latest findings on molecular determinants of viral pathogenicity, virus entry and cell tropism, pandemic risk assessment, transmission and pathogenesis in animal species, viral evolution, ecology and antigenic variation, while Volume II focuses on the role of innate and adaptive immunity in pathogenesis, development of vaccines and antivirals. 

The purpose of this review is to examine the potential role of molecular mimicry in the pathogenesis of human T-lymphotropic virus type 1 ((HTLV- 1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP)). Comp- hensive reviews on the pathogenic mechanisms of HTLV-1-associated human diseases are available throughout the medical literature (Bangham 2000,, 2003; Barmak et al. 2003; Jacobson 2002; Levin and Jacobson 1997; Nagai and Osame 2003; Osame 2002). Approximately 25 years ago the ?rst human retrovirus, HTLV-1, was isolated (Poeisz et al. 1980). Subsequently, infection with HTLV-1 was shown to cause adult T-cell leukemia (ATL) and HAM/TSP (Gessain et al. 1985; McFarlin and Blattner 1991; Osame et al. 1986; Poeisz et al. 1980; Yoshida et al. 1987). HTLV-1 may infect up to 30% of people in endemic areas and 10-20 million people worldwide (Barmak et al. 2003; Edlich et al. 2000). However, only 1%-5% develop either ATL or HAM/TSP, the remainder being clinically asymptomatic carriers of HTLV-1 (Bangham 2000, 2003; Barmak et al. 2003; Jacobson 2002; Levin and Jacobson 1997; Nagai and Osame 2003; Osame 2002). Why infection with HTLV-1 causes ATL or HAM/TSP in some people while the vast majority of individuals are asymptomatic is largely - known. Some possible factors that may differentiate the asymptomatic from the diseased state include viral strain, human histocompatibility leukocyte antigen (HLA), viral load, and the immune response (Bangham 2000, 2003; Barmak et al. 2003; Jacobson 2002; Levin and Jacobson 1997; Nagai and Osame 2003; Nagai et al. 1998; Niewiesk et al. 1994; Osame 2002).

Most diseases are multifactoral. Transgenic technology permits gene(s) of interest to be expressed in a small manipulatable laboratory animal model. By this process, murine models of human infections can be developed and studied; effects of cytokines in vivo, focally expressed in unique cells can be established and manipulated, and a variety of autoimmune disorders, mimicking human disease can be constructed. In this volume, these approaches for study of human immunodeficiency virus, hepatitis virus, viruses causing tumors and chronic degenerative disorders are described. Also included are chapters of transgenic models of autoimmune disorders like diabetes, systemic lupus and ankylosing spondylitis.

Cytotoxic T lymphocytes (CTL) control several viral infections in animals based on deletion and reconstitution experiments with CTL clones and use of CD8 genetically deficient (knock-out) mice. In this volume, data for the role that CTL play in human infectious diseases is presented. As such, this represents the first volume in which such information from several different viral and protozoan infections is brought together.

Reoviruses are one of the most important viral groups for understanding the molecular and genetic basis for viral pathogenesis. These two volumes cover virtually all aspects of reovirus biology. Volume I begins with a review of reovirus structure; further chapters deal with functions of the reovirus structural proteins, the assembly of the genome, and reovirus mutants. Volume II reviews general mechanisms of reovirus persistent infection and cytopathic effects, and then discusses reovirus-induced disease in specific organ systems including the heart, nervous and endocrine systems, liver and biliary system, and intestine. Together, these two volumes provide a current and comprehensive review of the mammalian reoviruses.

This volume focuses on the evidence for or against molecular mimicry as a cause of autoimmunity. Contributions from recognized experts present their original findings, and the final chapter reviews the overall perspective of molecular mimicry, how to use its principles in clinical investigation and list the conceptual traits by which autoimmune disaese can occur.

Leading researchers present contemporary treatment of in situ hybridization applied to current issues in animal virus pathogenesis. The most recent methods are given for locating viral genes in whole animal section and for defining the number and type of cells surrounded by viruses. The genetic programs played out in these cells and the newer methods of hybridization at the electron microscopic level provide valuable insight into the complexities of virus-host interaction.

M. B. A. OLDSTONE Viruses are generally studied either because they cause significant human, animal or plant disease or for their utility as materials to probe a basic phenomenon in biology, chemistry, genetics or molecular biology. Arenaviruses are unusually interesting in that they occupy both of these categories. Arenaviruses cause severe human diseases known primarily as the hemor rhagic fevers occurring in South and Latin America (Bolivia: Machupo virus and Argentina: Junin virus) and in Africa (Lassa virus). Because such viruses produce profound disability and may kill the persons they infect, they are a source of economic hardship in the countries where they are prevalent. Further, they provide new problems for health care personnel owing to the narrowing of the world as visitors from many countries increasingly travel to and from these endemic areas. In addition, lymphocytic choriomeningitis virus (LCMV) can infect humans worldwide, although the illness is most often less disabling than those elicited by other arenaviruses. Yet LCMV is likely of greater concern to non-arena-virologists and experimentalists using tissue culture or animals, i. e. , workers in molecular biology, cancer research, virology, immunobiology, etc. , because normal appearing cultured cells or tissues and animals used for research may be persistently infected with LCMV without manifesting clinical disease or cytopathology and transmit that infection to laboratory workers (reviewed OWSTONE and PETERS 1978). For example, HINMAN et al.

The National Institute of Mental Health (NIMH) AIDS Program is the fourth largest acquired immune deficiency syndrome (AIDS) program within the National Institutes of Health (NIH). Since 1983, our program's contributions have concentrated on two major areas. The first has been to develop effective strategies to prevent or reduce behaviors that place individuals at risk for human immunodeficiency virus type 1 (HIV-1) infection. The second has been to support and foster research to enhance our understanding of the profound impact of H IV-1 infection on the central nervous system (eNS). The brain appears to be a prime target of the virus and may serve as a reservoir for the virus. Post mortem examination of brain tissue has provided evidence of eNS cell damage in 80%-90% of people who die with AIDS. For about 10%-20% of people with AI DS, mild neuropsychological symptoms are the first signs of the disease. Approximately 20% of individuals infected with HIV-1 develop AIDS dementia complex. The symptoms include apathy, difficulty concentrat ing, irritability, depression, and personality changes. In the later stages of the disease, people may experience psychiatric disor ders. Death usually occurs within 6 months of the appearance of those more severe symptoms. Up to 90% of children infected with H IV-1 experience attention and concentration difficulties and often experience neurodevelopmental delay or regression over time."

The all new Concepts in Viral Pathogenesis III contains the widely praised format of presenting up-to-date information in pithy, easily read "mini-review" style and complements previous editions with contributions by leading international authorities on structure-function relationships, gene regulation, cell biology of viral infections, transgenic mice, expression of viral genes, retroviruses, and evolving concepts in viral diseases. Taken together, Volume I, II and III of Concepts in Viral Pathogenesis contain 145 unique chapters each representing the latest thinking in important areas of virology by the foremost investigators in the field. Clinicians, laboratory scientists, students, and others seeking authoritative overviews of current knowledge on the mechanism of viral diseases will welcome this valuable resource.

M. B. A. OLDSTONE Viruses are generally studied either because they cause significant human, animal or plant disease or for their utility as materials to probe a basic phenomenon in biology, chemistry, genetics or molecular biology. Arenaviruses are unusually interesting in that they occupy both of these categories. Arenaviruses cause severe human diseases known primarily as the hemor rhagic fevers occurring in South and Latin America (Bolivia: Machupo virus and Argentina: Junin virus) and in Africa (Lassa virus). Because such viruses produce profound disability and may kill the persons they infect, they are a source of economic hardship in the countries where they are prevalent. Further, they provide new problems for health care personnel owing to the narrowing of the world as visitors from many countries increasingly travel to and from these endemic areas. In addition, lymphocytic choriomeningitis virus (LCMV) can infect humans worldwide, although the illness is most often less disabling than those elicited by other arenaviruses. Yet LCMV is likely of greater concern to non-arena-virologists and experimentalists using tissue culture or animals, i. e. , workers in molecular biology, cancer research, virology, immunobiology, etc. , because normal appearing cultured cells or tissues and animals used for research may be persistently infected with LCMV without manifesting clinical disease or cytopathology and transmit that infection to laboratory workers (reviewed OLDSTONE and PETERS 1978). For example, HINMAN et al.

Reoviruses are one of the most important viral groups for understanding the molecular and genetic basis for viral pathogenesis. These two volumes cover virtually all aspects of reovirus biology. Volume I begins with a review of reovirus structure; further chapters deal with functions of the reovirus structural proteins, the assembly of the genome, and reovirus mutants. Volume II reviews general mechanisms of reovirus persistent infection and cytopathic effects, and then discusses reovirus-induced disease in specific organ systems including the heart, nervous and endocrine systems, liver and biliary system, and intestine. Together, these two volumes provide a current and comprehensive review of the mammalian reoviruses.