Influenza and genetics
Influenza, commonly known as the flu, is a contagious viral infection that primarily affects the respiratory system and is most prevalent during the winter months. Unlike the common cold, influenza can lead to more severe health complications, particularly in vulnerable populations such as young children, the elderly, and individuals with chronic health conditions. Historical evidence indicates that influenza pandemics have occurred periodically since the sixteenth century, with notable outbreaks in 1918, 1957, and 1968 resulting in millions of deaths worldwide.
At the genetic level, the influenza virus is composed of eight single-stranded RNA molecules, and it is categorized into three main types: A, B, and C. Type A is particularly concerning due to its ability to undergo significant genetic changes through mechanisms known as genetic drift and genetic shift, allowing it to create new strains that can evade previous immunity in the human population. Genetic shift often occurs in intermediate hosts like pigs, where different strains can reassort, leading to novel strains capable of causing pandemics.
Diagnosis is typically based on symptoms, and while antiviral medications can help manage the illness, prevention through annual vaccination remains one of the most effective strategies. In recent research, a gene named TDRD7 has been identified as a potential regulator against the influenza A virus, opening pathways for future therapeutic developments. Overall, understanding the interplay between influenza and genetics is crucial for anticipating outbreaks and developing effective public health responses.
Influenza and genetics
ALSO KNOWN AS: Flu; grippe; avian flu; swine flu
DEFINITION Influenza is a seasonal contagious viral disease that occurs most frequently in the winter. Influenza results in a respiratory infection that is more severe than the common cold. Historical evidence suggests that occasional, severe worldwide outbreaks (pandemics) have occurred every ten to forty years since the sixteenth century.
Risk Factors
The largest risk factor for contracting influenza is exposure to respiratory secretions of individuals with the illness. The virus is transmitted easily through aerosols caused by the coughing and sneezing of an infected person. Young children, elderly people, people with chronic health problems, and pregnant women are most at risk for influenza complications.
Etiology and Genetics
Influenza virus particles contain eight single-stranded RNA molecules that carry the genetic information necessary for the reproduction of the virus, surrounded by an outer membrane envelope. The surface of the virus is covered by two types of protruding protein spikes—the hemagglutinin (HA) protein that is responsible for the initial binding of the virus to a host cell receptor, the first step in the infection process, and the neuraminidase (NA) protein, an that is involved in release of virus particles from infected cells.
Human influenza viruses are divided into three antigenic types—A, B, and C. In addition to infecting humans, type A viruses also infect many species of animals, including ducks, chickens, pigs, horses, and dogs. Influenza strains that infect birds are sometimes called avian flu, and strains that infect pigs are sometimes called swine flu. Type B viruses only infect humans. Type C viruses infect humans and some other animals and cause only mild respiratory infections. Types A and B viruses can cause more severe illness, but type A is the most threatening to humans.
Type A influenza is the most adept at undergoing changes in its genetic makeup, giving it the ability to emerge as new, genetically distinct subtypes. The three global pandemics of the past century—the Spanish influenza in 1918, which killed about 50 million people, and the Asian (1957) and Hong Kong (1968) pandemics, which each killed 1 to 2 million people—were caused by new Type A influenza subtypes.
Sixteen HA serotypes and nine NA serotypes have been identified. Designation of the HA (H) and NA (N) serotypes define the type A subtype. The subtypes responsible for the 1918, 1957, and 1968 outbreaks were H1N1, H2N2, and H3N2, respectively. Type A influenza virus strains are named according to their type, the geographic location where they were first isolated, strain number, the year of isolation, and the subtype. For example, A/Sydney/5/97(H3N2) is strain 5 of an H3N2 subtype isolated in Sydney in 1997. There are no type B or C influenza subtypes.
Influenza viruses undergo more rapid genetic antigenic change than any other respiratory viruses. Two different genetic mechanisms—genetic drift and genetic shift—explain why influenza viruses change their genetic makeup so readily. Replication of single-strand RNA viruses is inherently more prone to error because the enzymatic steps involved in producing the requisite DNA intermediary have less fidelity than does the enzymatic machinery that copies DNA directly. This is the mechanism behind genetic drift. Small errors, or mutations, accumulate continuously. Occasionally, a random mutation will result in a structural change in the HA molecule, the part of the virus particle to which host antibodies most often bind. If that structural change results in a particular molecule no longer being able to bind to the virus particle, then that new virus can now escape the immunity mediated by that particular antibody.
Genetic shift is explained by the fact that some intermediate host animals, such as chickens or pigs, can be infected by different influenza A virus strains simultaneously. Susceptible pig cells have for avian and human influenza strains. If a pig is simultaneously infected by a bird strain and a human strain, for instance, then the genes from the two strains can mix, or reassort, to produce a new influenza strain containing genetic material from both the bird strain and the human strain. It is thought that the infection of humans by these types of novel strains is responsible for the rise of pandemic outbreaks. Since the reassorted strain is fundamentally new in nature, the human population has little, if any, residual resistance to it. As the virus continues to spread from human to human and to mutate, the strain may become even more virulent. The “swine flu” outbreak in the spring of 2009 was caused by a novel H1N1 influenza strain that was a triple genetic reassortment of swine, human, and avian strains.
In 2005, scientists reconstructed the 1918 pandemic influenza virus in the laboratory. The virus was an H1N1 strain of avian influenza that acquired the ability to infect humans. The H5N1 avian strain that caused widespread outbreaks in domestic poultry in Southeast Asia, and was the object of much concern earlier in the first decade of the twenty-first century, did not develop the ability to easily infect humans. Scientists are studying the molecular structure and binding specificities of the HA proteins from these and other influenza viruses, as well as their other genes and the mutations they contain, in an effort to understand what makes an influenza strain capable of causing a pandemic.
In 2022, researchers at the Icahn School of Medicine at Mount Sinai made a notable breakthrough in human genetic pathways related to the influenza virus. They identified the gene TDRD7 as a significant regulator against the influenza A virus. Scientists hoped to use this information iIn the future to develop new therapies and treatments for influenza.
Symptoms
Typical influenza symptoms include sore throat, cough, fever, body aches, muscle soreness, fatigue, weakness, headaches, chills, and sweats. Symptoms usually last for two to five days, although the illness may last for a week or more, and weakness and fatigue may last for several weeks.
Screening and Diagnosis
Influenza is usually diagnosed based on the typical symptoms that occur during flu season. When laboratory confirmation of diagnosis is desired, such as during a new outbreak, immunological tests are used to detect virus or viral antigens in upper respiratory samples taken from patients.
During the H1N1 outbreak in the spring of 2009, the US Centers for Disease Control and Prevention (CDC) posted comprehensive guidelines for the collection and diagnostic testing of samples from infected patients on its website. Samples were either shipped to the CDC for testing or tested at state public health departments with kits supplied by the CDC.
Treatment and Therapy
Treatment for influenza consists mainly of treating symptoms, including rest, drinking plenty of fluids, and over-the-counter products to relieve fever, headache, and muscle aches. Occasionally, serious complications of the flu can occur, the most common being pneumonia.
The antiviral agents amantadine and rimantadine can be used for both treatment and prevention of influenza infection, although influenza A viruses easily acquire resistance to both of these agents. In 2006, it was reported that 92 percent of influenza A viruses isolated from patients were resistant to amantadine. The neuraminidase inhibitors oseltamivir and zanamivir, which inhibit viral release from cells, are usually effective at treating influenza infections if they are used during the first forty-eight hours of illness.
Prevention and Outcomes
The influenza vaccine is one of the most effective ways to prevent infection. Each year, the three influenza strains thought to pose the most likely threat in the United States (usually two type A strains and one type B strain) are included in the annual vaccination program. Oseltamivir and zanamivir are effective in preventing infection, and their use is part of the contingency plan developed by the government to respond to a potential pandemic outbreak.
In the United States, complications of influenza result in the hospitalization of more than 200,000 people and the death of about 36,000 people each year.
Bibliography
Hampson, A. W., and J. S. Mackenzie. “The Influenza Viruses.” The Medical Journal of Australia 185, no. 10, suppl (2006): S39-43.
Hilleman, M. R. “Realities and Enigmas of Human Viral Influenza: Pathogenesis, Epidemiology, and Control.” Vaccine 20 (2002): 3068-3087.
"Researchers Identify Flu-Fighting Pathways and Genes Essential for Influenza A Immune Defense." Mount Sinai, 5 Oct. 2022, www.mountsinai.org/about/newsroom/2022/researchers-identify-flu-fighting-pathways-and-genes-essential-for-influenza-a-immune-defense. Accessed 4 Sept. 2024.
Tan, James S., Thomas M. File, Jr., Robert A. Salata, and Michael J. Tan. Infectious Diseases. 2d ed. Philadelphia: ACP Press, 2008.