Pathogenicity And Transmissibility Of Novel Influenza Viruses

Influenza A virus (IAV) is an enveloped, segmented, negative-sense RNA virus that infects avian species and mammals. Its segmented feature enables antigenic shift which can generate novel IAVs that pose a threat to animal and public health due to lack of immunity to these viruses. Pigs have been considered the "mixing vessels" of influenza A viruses to generate novel reassortant viruses that may threaten animal and public health. Therefore, it is necessary to understand the pathogenicity and transmissibility of newly emerged reassortant viruses in swine. Adding to this complexity is the newly identified bat influenza A-like viruses which have roused interest in understanding the evolutionary history and pandemic potential of bat influenza. At least 10 different genotypes of novel reassortant H3N2 IAVs with gene(s) from 2009 pandemic H1N1 [A(H1N1)pdm09] have been identified in pigs in the United States. To date, only three genotypes of these viruses have been evaluated in animal models leaving the pathogenicity and transmissibility of the other seven genotype viruses unknown. We showed that reassortant viruses with genes from A(H1N1)pdm09 are pathogenic and transmissible in pigs. Further studies showed that avian-like glycine at position 228 of the HA receptor binding site is responsible for inefficient transmission of the reassortant H3N2 IAV with five A(H1N1)pdm09 genes. Studying the recently discovered IAV-like sequences from bats has been hindered by the lack of live virus isolation or culturing. Using synthetic genomics, we successfully rescued modified bat influenza viruses that had the HA and NA coding regions replaced with two classical IAVs. Additional studies were performed with truncations on NS1 protein and substitution of a putative virulence mutation in bat influenza PB2. Virus reassortment experiments demonstrated that bat influenza has limited genetic and protein compatibility with other influenza viruses; however, it readily reassorts with another divergent bat influenza virus. Taken together, our results provide insights into the pathogenicity and transmissibility of novel reassortant H3N2 IAVs in pigs. It also indicates that the bat influenza viruses recently identified are viable viruses that pose little pandemic threat to humans. Moreover, they provide new insights into the evolution and basic biology of influenza viruses.

When, in late 2011, it became public knowledge that two research groups had submitted for publication manuscripts that reported on their work on mammalian transmissibility of a lethal H5N1 avian influenza strain, the information caused an international debate about the appropriateness and communication of the researchers' work, the risks associated with the work, partial or complete censorship of scientific publications, and dual-use research of concern in general. Recognizing that the H5N1 research is only the most recent scientific activity subject to widespread attention due to safety and security concerns, on May 1, 2012, the National Research Council's Committee on Science, Technology and Law, in conjunction with the Board on Life Sciences and the Institute of Medicine's Forum on Microbial Threats, convened a one-day public workshop for the purposes of 1) discussing the H5N1 controversy; 2) considering responses by the National Institute of Allergy and Infectious Diseases (NIAID), which had funded this research, the World Health Organization, the U.S. National Science Advisory Board for Biosecurity (NSABB), scientific publishers, and members of the international research community; and 3) providing a forum wherein the concerns and interests of the broader community of stakeholders, including policy makers, biosafety and biosecurity experts, non-governmental organizations, international organizations, and the general public might be articulated. Perspectives on Research with H5N1 Avian Influenza: Scientific Enquiry, Communication, Controversy summarizes the proceedings of the workshop.

Public health officials and organizations around the world remain on high alert because of increasing concerns about the prospect of an influenza pandemic, which many experts believe to be inevitable. Moreover, recent problems with the availability and strain-specificity of vaccine for annual flu epidemics in some countries and the rise of pandemic strains of avian flu in disparate geographic regions have alarmed experts about the world's ability to prevent or contain a human pandemic. The workshop summary, The Threat of Pandemic Influenza: Are We Ready? addresses these urgent concerns. The report describes what steps the United States and other countries have taken thus far to prepare for the next outbreak of "killer flu." It also looks at gaps in readiness, including hospitals' inability to absorb a surge of patients and many nations' incapacity to monitor and detect flu outbreaks. The report points to the need for international agreements to share flu vaccine and antiviral stockpiles to ensure that the 88 percent of nations that cannot manufacture or stockpile these products have access to them. It chronicles the toll of the H5N1 strain of avian flu currently circulating among poultry in many parts of Asia, which now accounts for the culling of millions of birds and the death of at least 50 persons. And it compares the costs of preparations with the costs of illness and death that could arise during an outbreak.

In November 2018, an ad hoc planning committee at the National Academies of Sciences, Engineering, and Medicine planned two sister workshops held in Washington, DC, to examine the lessons from influenza pandemics and other major outbreaks, understand the extent to which the lessons have been learned, and discuss how they could be applied further to ensure that countries are sufficiently ready for future pandemics. This publication summarizes the presentations and discussions from both workshops.

This book provides salient information on all aspects of influenza/flu viruses affecting animals and humans. It specifically reviews the properties and replication of influenza viruses; their evolution and emergence; epidemiology; role of migratory birds in disease transmission; clinical signs in humans, animals and poultry; pathogenesis and pathogenicity; public health importance and potential threats; diagnosis; prevention and control measures; and pandemic preparedness. Influenza/flu viruses evolve continuously and jump species causing epidemics as well as pandemics in both human and animals. During the past 150 years, various strains of influenza virus like the Spanish flu, Asian flu, Hong Kong flu, bird flu and swine flu were responsible for high mortality in humans as well as birds. High mutation rates, antigenic shifts, drifts, reassortment phenomena, and the development of antiviral drug resistance all contribute to ineffective chemotherapy and vaccines against influenza viruses. Due to their devastating nature, high zoonotic implications and high mortality in humans and poultry, they have a severe impact on the socioeconomic status of countries. Disease awareness, rapid and accurate diagnosis, surveillance, strict biosecurity, timely adoption of appropriate preventive and control measures and pandemic preparedness are crucial to help reduce virus transmission, thus reducing clinical cases, deaths and pandemic threats.

Veteran journalist Gina Kolata's Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It presents a fascinating look at true story of the world's deadliest disease. In 1918, the Great Flu Epidemic felled the young and healthy virtually overnight. An estimated forty million people died as the epidemic raged. Children were left orphaned and families were devastated. As many American soldiers were killed by the 1918 flu as were killed in battle during World War I. And no area of the globe was safe. Eskimos living in remote outposts in the frozen tundra were sickened and killed by the flu in such numbers that entire villages were wiped out. Scientists have recently rediscovered shards of the flu virus frozen in Alaska and preserved in scraps of tissue in a government warehouse. Gina Kolata, an acclaimed reporter for The New York Times, unravels the mystery of this lethal virus with the high drama of a great adventure story. Delving into the history of the flu and previous epidemics, detailing the science and the latest understanding of this mortal disease, Kolata addresses the prospects for a great epidemic recurring, and, most important, what can be done to prevent it.

The Textbook of Influenza is a comprehensive resource covering all aspects of influenza, from the genetic and molecular biology of the virus through to clinical aspects of the disease and the latest drug developments and treatments. This new edition has been completely revised and reflects the integration of disciplines concerning the emergence, evolution, pathogenesis and control of influenza viruses in the field of human and veterinary public health. Textbook of Influenza examines the lessons learnt from the latest pandemic and provides the current state of knowledge for many yet unresolved issues related to virus origin, spread, pathogenesis and disease severity to better prepare for future pandemics. It covers the background to recent advances in influenza genomics and reverse genetics which have allowed the identification of virus virulence factors and the analysis and reconstruction of influenza viruses such as the 1918 Spanish flu strain. This new edition is divided into eight key sections, containing chapters co-written by international experts from both the clinical and scientific communities, covering: • Influenza Perspectives • Structure and Replication • Evolution and Ecology • Epidemiology and Surveillance • Immunology • Vaccines and Vaccine Development • Clinical Aspects and Antivirals • Public Health Textbook of Influenza is for all those working in the area of influenza including clinical and basic scientists, immunologists, molecular and structural virologists, public health officials and global pandemic control planners.