Specific varieties of the virus are generally named according to the particular antigenic determinants of hemagglutinin 13 major types and neuraminidase 9 major types surface proteins they possess, as in influenza A H2N1 and A H3N2. New strains of the influenza virus emerge due to a gradual process known as antigenic drift , in which mutations within the virus antibody-binding sites accumulate over time.
Through this mechanism, the virus is able to largely circumvent the body's immune system, which may not be able to recognize and confer immunity to a new influenza strain even if an individual has already built up immunity to a different strain of the virus.
Both A and B influenza viruses continually undergo antigenic drift, but the reformulation of influenza vaccines each year often enables scientists to take into account any new strains that have emerged.
Influenza A also experiences another type of mutation called antigenic shift that results in a new subtype of the virus. Antigenic shift is a sudden change in antigenicity caused by the recombination of the influenza genome, which can occur when a cell becomes simultaneously infected by two different strains of type A influenza. The unusually broad range of hosts susceptible to influenza A appears to increase the likelihood that this event will occur.
In particular, the mixing of strains that can infect birds, pigs, and humans is thought to be responsible for most antigenic shifts. Notably, in some parts of the world, humans live in close proximity to both swine and fowl, so that human strains and bird strains, may readily infect a pig at the same time, resulting in a unique virus. New subtypes of influenza A develop abruptly and unpredictably so that scientists are unable to prepare vaccines in advance that are effective against them.
Consequently, the emergence of a new subtype of the virus can cause a global pandemic in a very short amount of time. In addition to vaccines, a few other weapons have been designed to combat the flu. The antiviral medications amantadine and rimantadine can help reduce severity of illness in individuals with influenza that begin utilizing the drugs within two days of the onset of symptoms. These drugs work by hindering the change in pH that is necessary for the flu virion to release its contents into the cytosol of a host cell.
Two additional antiviral drugs, zanamavir and oseltamivir, are effective against both A and B types of influenza. Instead of interfering with pH shifts, zanamavir and oseltamivir block the glycoprotein neuraminidase so that the release of new virus particles is inhibited and their spread is thwarted. The outbreak peaked in October of , with flu activity reported in all 50 states, as well as numerous other countries and territories.
By January , flu activity had returned to below baseline levels. The H1N1 virus continues to circulate at low levels, but it is no longer the dominant influenza strain, and its behavior more closely resembles a seasonal influenza virus than a pandemic flu. From the time the outbreak began in April through April , the CDC estimated that about 60 million Americans became infected with the H1N1 virus, , Americans were hospitalized and 12, deaths occurred as a consequence of the H1N1 flu.
The highest hospitalization rates occurred in young children. Exact numbers are not known due to the widespread nature of the outbreak and because most patients, especially those with mild cases, were not tested.
The large majority of infections in the United States and most other countries were mild, although pregnant women and individuals with certain underlying medical conditions had an increased risk of severe and fatal illness.
There were some differences between the pandemic H1N1 flu and regular, seasonal flu. First, the H1N1 flu continued to spread during the summer months, which is uncommon for seasonal flu.
Second, a much larger percentage of H1N1 patients exhibited symptoms of vomiting and diarrhea than is common with regular seasonal flu. There were also more reports of severe respiratory disease, especially in young and otherwise healthy people, infected with the new H1N1 virus than with seasonal flu viruses.
Significantly, the majority of cases of H1N1 infection, including severe and fatal cases, occurred in young and otherwise healthy individuals generally between the ages of 5 and 50, with relatively few deaths among the elderly.
This is in contrast to the situation with seasonal flu which primarily afflicts the very young and the elderly, and where 90 percent of severe and lethal cases occur in people over the age of Deaths among the elderly accounted for only 11 percent of H1N1 deaths.
Proper use of these drugs can shorten the duration and lessen the severity of the sickness and reduce the chance of spreading the disease. The drugs reduce the risk of pneumonia - a major cause of death from influenza - and the need for hospitalization. To be most effective, the antiviral drugs should be administered as soon as possible after the onset of symptoms. A vaccine to protect against the H1N1 virus was developed, tested, and approved and became available in October Due to the fact that the virus used to prepare the vaccine grew more slowly than most seasonal flu viruses do, production of the vaccine lagged and widespread distribution of the vaccine occurred later than anticipated.
Priority for the vaccine was initially given to health care and emergency workers and individuals at high risk for severe disease, but by the winter of availability was extended to the general population. Later, some doses went unused. Although some had concerns about the safety of the H1N1 vaccine, flu vaccines have a very good safety profile. While mild side effects, such as soreness at the site of injection, aches, and low-grade fever, may occur as a result of receiving a flu shot, it is not possible to get the flu H1N1 or seasonal from the vaccine.
The flu shot, or inactivated vaccine, is made from only a portion of the virus — a purified protein that makes our immune system develop protection. Likewise, the nasal spray version of the flu vaccine contains attenuated or weakened virus that is not able to cause the flu.
Given the potential serious health outcomes from the flu, especially for high-risk population groups, the benefits of vaccination as the best way to prevent influenza infection and its complications far outweigh the risk of relatively minor side effects from the vaccination.
Historically, influenza pandemics arise about three to four times each century. The most recent pandemic , and the first of the 21st century, occurred in , some 40 years after the previous pandemic.
The H1N1 flu, commonly known as swine flu, spread around the globe faster than any virus in history, largely due to air travel. Pandemic flu strains are of deep concern because there is no or only limited natural immunity to novel flu strains, and therefore nearly everyone is susceptible to infection. A high percentage of the population could become ill at any one time and overwhelm public health systems, and a large number of deaths could occur.
We were very fortunate in the case of the H1N1 pandemic. Most people suffered only a mild illness. H1N1 was not an especially virulent virus. Further, the virus remained stable and did not mutate to a more deadly form or to a drug resistant form. Other influenza strains have been far more lethal. Currently, there is concern about the new avian H7N9 virus. Most patients have experienced severe respiratory illness, with about one-third of the cases resulting in death.
Although the virus does not appear to pass easily from person to person, there is always the worry that it could mutate into a form that is more transmissible. There are drugs that are effective against influenza, but the possibility that a virus could acquire resistance to the drugs is a serious issue.
There are four different antiviral drugs, of two different classes, that are effective against influenza. However, influenza viruses can and do develop resistance to these drugs - as one of the main circulating seasonal viruses did during a recent flu season - so that the drugs can no longer be used to treat or prevent infections. There is a need to develop additional drugs that can prevent or alleviate flu symptoms. Vaccines can be developed to protect humans from influenza viruses.
However, as was strikingly obvious during the H1N1 pandemic, vaccine production takes many months. By the time a vaccine was developed, tested, produced, and distributed, many individuals had already been infected.
Clearly, a more rapid method of vaccine development is needed. The goal of developing a universal flu vaccine, one that would provide durable protection against multiple flu strains, remains a challenging feat. The greatest fear is that a new pandemic influenza virus could emerge that could pass from person to person as easily as the H1N1 virus, but be as deadly as the H5N1 virus. Additional concerns are that an influenza virus could mutate into a form that would be resistant to anti-influenza drugs, such as Tamiflu, or that the virus could change so that a vaccine no longer afforded protection.
Even though the H1N1 pandemic was relatively mild, knowing how lethal and unpredictable influenza viruses can be, we must continue to remain alert and prepare for future pandemics. Investigators in the Department of Molecular Virology and Microbiology MVM have been studying influenza for several decades, with an Influenza Research Center first established in A major focus of the work is directed towards the development and testing of influenza vaccines to find the most effective vaccination dosages, methods, and strategies to protect the population against this deadly disease.
Other projects involve studying the structure and function of important influenza proteins. Research is ongoing on both epidemic influenza also referred to as seasonal or interpandemic influenza and pandemic influenza. Epidemic influenza occurs annually and is attributable to minor changes in genes that encode proteins on the surface of circulating influenza viruses. Pandemic influenza occurs when more significant changes in the influenza A virus arise as a result of the acquisition of genes from influenza viruses of other animal species by a human virus strain, thus creating a novel virus.
The latter carries a greater risk for the human population. It was previously led by Dr. Wendy Keitel and is currently under the direction of Dr. Hana El-Sahly. The VTEU network conducts clinical trials that evaluate vaccines and treatments for a wide array of infectious diseases. An important strength of this established network is that it is able to efficiently and safely test new vaccines within a rapid time frame.
The VTEU research group in the department has been involved in important studies that led to the licensure of live attenuated and high dose inactivated influenza virus vaccines. They have tested vaccines to seasonal influenza and they have performed many studies evaluating vaccines targeting pandemic influenza, including the swine-origin H1N1, and the H5N1, H9N2, and H7N9 viruses, among others. They have evaluated methods to improve vaccine immunogenicity, including delivery of vaccine by different routes of administration, different dosages, and with different adjuvant preparations.
Researchers involved in these studies include Drs. Their hope is that the results of these studies will identify the optimal and most effective dosages of vaccine to protect the public from seasonal influenza, as well as from a possible influenza pandemic. MVM investigators would like to better understand epidemic influenza seasonal flu infections, disease, and vaccines with the goal of developing ways to better control these epidemics.
The rod shape is due to the linear array of the nucleic acid and the protein subunits making up the capsid.
The sphere shape is actually a sided polygon icosahedron. The nature of viruses wasn't understood until the twentieth century, but their effects had been observed for centuries. British physician Edward Jenner even discovered the principle of inoculation in the late eighteenth century, after he observed that people who contracted the mild cowpox disease were generally immune to the deadlier smallpox disease. By the late nineteenth century, scientists knew that some agent was causing a disease of tobacco plants, but would not grow on an artificial medium like bacteria and was too small to be seen through a light microscope.
Advances in live cell culture and microscopy in the twentieth century eventually allowed scientists to identify viruses. Advances in genetics dramatically improved the identification process. Capsid - The capsid is the protein shell that encloses the nucleic acid; with its enclosed nucleic acid, it is called the nucleocapsid. This shell is composed of protein organized in subunits known as capsomers. They are closely associated with the nucleic acid and reflect its configuration, either a rod-shaped helix or a polygon-shaped sphere.
The capsid has three functions: 1 it protects the nucleic acid from digestion by enzymes, 2 contains special sites on its surface that allow the virion to attach to a host cell, and 3 provides proteins that enable the virion to penetrate the host cell membrane and, in some cases, to inject the infectious nucleic acid into the cell's cytoplasm.
Under the right conditions, viral RNA in a liquid suspension of protein molecules will self-assemble a capsid to become a functional and infectious virus. Envelope - Many types of virus have a glycoprotein envelope surrounding the nucleocapsid. The envelope is composed of two lipid layers interspersed with protein molecules lipoprotein bilayer and may contain material from the membrane of a host cell as well as that of viral origin.
The virus obtains the lipid molecules from the cell membrane during the viral budding process. However, the virus replaces the proteins in the cell membrane with its own proteins, creating a hybrid structure of cell-derived lipids and virus-derived proteins.
Many viruses also develop spikes made of glycoprotein on their envelopes that help them to attach to specific cell surfaces. Nucleic Acid - Just as in cells, the nucleic acid of each virus encodes the genetic information for the synthesis of all proteins.
Full Sized Infographic and Text Version. Genome sequencing reveals the sequence of the nucleotides in a gene, like alphabet letters in words. Comparing the composition of nucleotides in one virus gene with the order of nucleotides in a different virus gene can reveal variations between the two viruses. Proteins are made of sequences of amino acids. The substitution of one amino acid for another can affect properties of a virus, such as how well a virus transmits between people, and how susceptible the virus is to antiviral drugs or current vaccines.
CDC and other public health laboratories around the world have been sequencing the gene segments of influenza viruses since the s. The sequences deposited into these databases allow CDC and other researchers to compare the genes of currently circulating influenza viruses with the genes of older influenza viruses and those used in vaccines. This process of comparing genetic sequences is called genetic characterization. CDC uses genetic characterization for several reasons:.
Each sequence from a specific influenza virus has its own branch on the tree. Viruses are grouped by comparing changes in nucleotides within the gene. Viruses which share a common ancestor can also be described as belonging to the same clade. The degree of genetic difference number of nucleotide differences between viruses is represented by the length of the horizontal lines branches in the phylogenetic tree. The further apart viruses are on the horizontal axis of a phylogenetic tree, the more genetically different the viruses are to one another.
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