![]() ![]() (RNA viruses in particular are not transmitted to multiple cells as identical virions, but as collections of thousands of different genetically related virions. ![]() Host-switching determinants prominently include social, environmental, and biological factors providing the opportunity for host–species interaction shared host cell receptors genetic distance between transmitting and receiving hosts and characteristics and complexity of the viral quasi-species or viral swarm. ![]() 5 The complex genetic events that underlie host-switching differ greatly from pathogen to pathogen, but general mechanisms have been recognized for many. Most of the human viral and nonviral infectious diseases that have existed for centuries-measles, influenza, cholera, smallpox (eradicated in 1980), falciparum malaria, 4 dengue, HIV, and many others-originated by animal-to-human host-switching. Emergence of a pathogen between a vertebrate or an insect has been referred to as host-switching, sometimes described as a spillover event. It follows that when a virus enters a human cell for the first time, it has very recently been transmitted from cells of some other host, that is, from another animal or, for example, an insect vector. Viruses are therefore nonliving self-contained genetic programs capable of redirecting a cell’s machinery to produce more of themselves. Viruses are not living organisms and can only reproduce inside living cells susceptible to viral entry and with the capacity to replicate viral nucleic acids and translate nucleic acid signals into amino acids to build viral proteins. Viruses are compact nucleic acid packages of either DNA or (in the case of coronaviruses) RNA associated with proteins, and in some cases with lipids. In addition to controlling the COVID-19 pandemic, we must undertake vigorous scientific, public health, and societal actions, including significantly increased funding for basic and applied research addressing disease emergence, to prevent this tragic history from repeating itself. The risk of similar coronavirus outbreaks in the future remains high. Unfortunately, few such preventive actions were taken resulting in the latest coronavirus emergence detected in late 2019 which quickly spread pandemically. Scientists have warned for decades that such sarbecoviruses are poised to emerge again and again, identified risk factors, and argued for enhanced pandemic prevention and control efforts. Nevertheless, a large body of virologic, epidemiologic, veterinary, and ecologic data establishes that the new virus, SARS-CoV-2, evolved directly or indirectly from a β-coronavirus in the sarbecovirus (SARS-like virus) group that naturally infect bats and pangolins in Asia and Southeast Asia. As with all past pandemics, the specific mechanism of its emergence in humans remains unknown. Taubenberger, Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, E-mail: COVID-19 pandemic is among the deadliest infectious diseases to have emerged in recent history. Monath, Crozet BioPharma LLC, Devens, MA, E-mail: Jeffery K. Kramer, Wadsworth Center, New York State Department of Health, Albany, NY, E-mail: James LeDuc, University of Texas Medical Branch, Galveston, TX, E-mail: Thomas P. Keusch, Boston University School of Medicine, Boston, MA, E-mail: Laura D. Hahn, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, E-mail: Gerald T. Doherty, Department of Microbiology and Immunology, University of Melbourne at the Doherty Institute, Melbourne, Australia, E-mail: Beatrice H. Calisher, Colorado State University, Fort Collins, CO, E-mail: Peter C. Breman, American Society of Tropical Medicine and Hygiene, Arlington, VA, E-mail: Charles H. Morens, American Committee on Arthropod-Borne Viruses, American Society of Tropical Medicine and Hygiene, Arlington, VA, and National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, E-mail: Joel G. ![]()
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