# Potential Links Between the Wuhan Institute of Virology and the Origin of the COVID-19 Pandemic/Appendix A

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​(U) APPENDIX A: DEFINITIONS
(U) Antibody: A protein produced during an immune response to a part of an infectious agent called an antigen.
(U) Backbone: A genetic sequence used as a chassis upon which to build synthetic constructs, such as those used for cloning, protein expression, and production.
(U) Biosafety: The application of knowledge, techniques, and equipment to prevent personal, laboratory, and environmental exposure to potentially infectious agents or biohazards. Four Biosafety levels (BSL) define the containment conditions under which biological agents can be safely manipulated. These standards range from moderate safety requirements for low-risk agents (BSL-1), to the most stringent controls for high-risk agents (BSL-4). China’s standards range from P1–4.
(U) Biosecurity: The protection, control of, and accountability for biological agents, toxins, and biological materials and information to prevent unauthorized possession, loss, theft, misuse, diversion, and accidental or intentional release.
(U) Coronavirus: A family of common viruses that can infect humans and/or animals. The human illness caused by most coronaviruses usually lasts a short time and presents symptoms consistent with the “common cold,” such as a runny nose, sore throat, cough, and fever.
(U) COVID-19: An infectious disease caused by the SARS-CoV-2 virus, which is a betacoronavirus.
(U) Diagnostic Information: Information that allows IC analysts to distinguish between hypotheses—in this case, the laboratory origin and natural origin theories.
(U) DNA (deoxyribonucleic acid): A molecule that carries an organism’s genetic blueprint for growth, development, function, and reproduction.
(U) Gain-of-function: The IC considers this as a research method that involves manipulating an organism’s genetic material to impart new biological functions that could enhance virulence or transmissibility (e.g., genetically modifying a virus to expand its host range, transmissibility, or severity of illness). The IC assesses that genetic engineering, genetic modification, and laboratory-adaptation can all be used for gain-of-function experiments, but are not inherently so.
(U) Genetically engineered or genetically modified viruses are intentionally altered, created, or edited using biotechnologies, such as Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR), DNA recombination, or reverse genetics. These viruses have intentional, targeted edits to the genome designed to achieve specific results, but unintentional genomic changes may also occur.
(U) Genome: The genetic material of an organism. It consists of DNA (and sometimes RNA for viruses).
​(U) Genome sequencing: The process of determining the DNA or RNA sequence of an organism’s genome, or its “genetic code.” An organism’s genetic code is the order in which the four nucleotide bases—adenine, cytosine, guanine, and thymine—are arranged to direct the sequence of the 20 different amino acids in the proteins that determine inherited traits.
(U) Intermediate species/host: An organism that can be infected with a pathogen from a reservoir species and passes the pathogen to another host species; infection is not sustained in this population.
(U) Laboratory-adapted viruses have undergone natural, random mutations through human-enabled processes in a laboratory—such as repeated passage through animals or cells—that put pressure on the virus to more rapidly evolve. Specific changes to the viral genome are not necessarily anticipated in these processes, though the virus can be expected to gain certain characteristics, such as the ability to infect a new species. This is a common technique used in public health research of viruses. We consider directed evolution to be under laboratory adaptation.
(U) Laboratory-associated incidents include incidents that happen in biological research facilities or during research-related sampling activities.
(U) Naturally occurring viruses have not been altered in a laboratory. Viruses commonly undergo random mutations as part of the evolutionary process and can continue to change over time; mutations may enable a virus to adapt to its environment, such as evading host immune responses and promoting viral replication.
(U) Outbreak: A sudden increase in occurrences of a disease in a particular time and place. Outbreaks include epidemics, which is a term that is reserved for infectious diseases that occur in a confined geographical area. Pandemics are near-global disease outbreaks.
(U) Pangolin: An African and Asian mammal that has a body covered in overlapping scales. Pangolins are a natural reservoir of coronaviruses and researchers are investigating their potential role as an intermediate host for the COVID-19 virus.
(U) Pathogen: A bacterium, virus, or other microorganism that can cause disease.
(U) Progenitor Virus: A virus that is closely related enough—more than 99 percent—to SARS-CoV-2 to have been its direct ancestor or plausible immediate origin of the outbreak. The closest known relative to SARS-CoV-2 is only about 96 percent similar; to put this into context, humans and chimps are about 99 percent similar, demonstrating the significant differences even at this similarity.
(U) Reverse genetics: A process for determining the natural function of genes by introducing mutations and studying the effect of those mutations.
​(U) RNA (ribonucleic acid): A molecule essential for gene coding, decoding, regulation, and expression. The genome of certain viruses, including coronaviruses, is made of RNA rather than DNA.
(U) Virus: A replicating piece of genetic material—DNA or RNA—and associated proteins that use the cellular machinery of a living cell to reproduce.
(U) Zoonosis: An infection or a disease that is transmissible from animals to humans under natural conditions. A zoonotic pathogen may be viral, bacterial, or parasitic, and can sometimes be transmitted through insects, such as mosquitoes.
(U) Zoonotic spillover: An initial infection or disease that is caused by contact between an animal and human under natural conditions.