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Myocarditis and inflammatory cardiomyopathy: current evidence and future directions
Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.
Journal Article
The long noncoding RNA Lnczc3h7a promotes a TRIM25-mediated RIG-I antiviral innate immune response
The helicase RIG-I initiates an antiviral immune response after recognition of pathogenic RNA. TRIM25, an E3 ubiquitin ligase, mediates K63-linked ubiquitination of RIG-I, which is crucial for RIG-I downstream signaling and the antiviral innate immune response. The components and mode of the RIG-I-initiated innate signaling remain to be fully understood. Here we identify a novel long noncoding RNA (Lnczc3h7a) that binds to TRIM25 and promotes RIG-I-mediated antiviral innate immune responses. Depletion of Lnczc3h7a impairs RIG-I signaling and the antiviral innate response to RNA viruses in vitro and in vivo. Mechanistically, Lnczc3h7a binds to both TRIM25 and activated RIG-I, serving as a molecular scaffold for stabilization of the RIG-I-TRIM25 complex at the early stage of viral infection. Lnczc3h7a facilitates TRIM25-mediated K63-linked ubiquitination of RIG-I and thus promotes downstream signaling transduction. Our findings reveal that host RNAs can enhance the response of innate immune sensors to foreign RNAs, ensuring effective antiviral defense.
Journal Article
Bat-borne virus diversity, spillover and emergence
Most viral pathogens in humans have animal origins and arose through cross-species transmission. Over the past 50 years, several viruses, including Ebola virus, Marburg virus, Nipah virus, Hendra virus, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory coronavirus (MERS-CoV) and SARS-CoV-2, have been linked back to various bat species. Despite decades of research into bats and the pathogens they carry, the fields of bat virus ecology and molecular biology are still nascent, with many questions largely unexplored, thus hindering our ability to anticipate and prepare for the next viral outbreak. In this Review, we discuss the latest advancements and understanding of bat-borne viruses, reflecting on current knowledge gaps and outlining the potential routes for future research as well as for outbreak response and prevention efforts.
Journal Article
The end of plagues : the global battle against infectious disease
\"At the turn of the twentieth century, smallpox claimed the lives of two million people per year. By 1979, the disease had been eradicated and victory was declared across the globe. Yet the story of smallpox remains the exception, as today a host of deadly contagions, from polio to AIDS, continue to threaten human health around the world. Spanning three centuries, The End of Plagues weaves together the discovery of vaccination, the birth and growth of immunology, and the fight to eradicate the world's most feared diseases. From Edward Jenner's discovery of vaccination in 1796, to the early nineteenth-century foundling voyages in which chains of orphans, vaccinated one by one, were sent to colonies around the globe, to the development of polio vaccines and the stockpiling of smallpox as a biological weapon in the Cold War, world-renown immunologist John Rhodes charts our fight against these plagues, and shows how vaccinations gave humanity the upper hand. Today, aid groups including the Bill and Melinda Gates Foundation and the World Health Organization have made the eradication of polio a priority, and Rhodes takes us behind the scenes to witness the hard-fought battles of scientist, philanthropists, volunteers, and more, and how soon we may be celebrating the eradication of a second infectious disease, polio\"--Provided by publisher.
Book
Nonhuman primate models of human viral infections
Humans have a close phylogenetic relationship with nonhuman primates (NHPs) and share many physiological parallels, such as highly similar immune systems, with them. Importantly, NHPs can be infected with many human or related simian viruses. In many cases, viruses replicate in the same cell types as in humans, and infections are often associated with the same pathologies. In addition, many reagents that are used to study the human immune response cross-react with NHP molecules. As such, NHPs are often used as models to study viral vaccine efficacy and antiviral therapeutic safety and efficacy and to understand aspects of viral pathogenesis. With several emerging viral infections becoming epidemic, NHPs are proving to be a very beneficial benchmark for investigating human viral infections.
Journal Article
Thunder and ashes
\"A lot can change in three months: Wars can be decided, nations can be forged...or entire species can be brought to the brink of annihilation. The Morningstar virus has swept the face of the planet, infecting billions. It hosts rampage; its victims don't die, but are reborn as cannibalistic shamblers. Scattered across the world, embattled groups have persevered. For some, survival is the pinnacle of achievement. Others hoard goods and weapons. And still others leverage power over the remnants of humanity with a mysterious cure. Francis Sherman and Anna Demilio want only a vaccine, but to find it they must cross a ravaged landscape of the infected and the lawless living. The bulk of the storm has passed, leaving echoing thunder and softly drifting ashes. But for the survivors, the peril remains, and the search for a cure is just beginning...\"--P. [4] of cover.
Book
Defining B cell immunodominance to viruses
Immunodominance (ID) defines the hierarchical immune response to competing antigens in complex immunogens. Little is known regarding B cell and antibody ID despite its importance in immunity to viruses and other pathogens. We show that B cells and serum antibodies from inbred mice demonstrate a reproducible ID hierarchy to the five major antigenic sites in the influenza A virus hemagglutinin globular domain. The hierarchy changed as the immune response progressed, and it was dependent on antigen formulation and delivery. Passive antibody transfer and sequential infection experiments demonstrated 'original antigenic suppression', a phenomenon in which antibodies suppress memory responses to the priming antigenic site. Our study provides a template for attaining deeper understanding of antibody ID to viruses and other complex immunogens.
Journal Article