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Influenza (Virus)

About || Signs and Symptoms || Diagnosis || Treatment || Overview ||
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About





Influenza is a common virus of the orthomyxovirus family. They are enveloped, single-stranded, segmented, negative-sense RNA viruses (try saying that five times fast!).

Influenza virus is one of only two RNA viruses that replicate in the nucleus of the cell (the other being retroviruses). Given that influenza viruses have negative-sense RNA genomes they must carry their own copy of RNA-dependent RNA-polymerase. This enzyme allows them to convert their negative-sense RNA into positive-sense RNA, which can be used to create viral proteins.

All influenza viruses contain two important proteins on their surfaces. The first protein is called hemagglutinin. Hemagglutinin is a glycoprotein (ie: a protein with sugar molecules attached to it). It binds to a sugar residue on human cells known as sialic acid. Once bound, hemagglutinin helps influenza infect the target cell.

The second important molecule is neuraminidase. Neuraminidase allows newly formed virus particles to bud off of an infected cell. It does this by cleaving glycosidic bonds (ie: bonds that connect one sugar to another molecule).

Both hemagglutinin and neuraminidase are the target of the human immune response responsible for fighting infection. Antibodies to these two proteins develop and help neutralize the virus.

There are three types of influenza that infect humans: type A, B, and C. The different types of influenza are based on the host(s) they infect, as well as the number of RNA molecules and proteins they make. Certain types also have the ability to undergo radical genetic shifts.

Type A influenza is categorized based on the type of neuraminidase and hemagglutinin that their RNA encodes. For example, influenza "H1N1", which stands for hemagglutinin type 1 and neuraminidase type 1, was responsible for the Spanish flu of 1918. Type A virus infects multiple hosts including humans, birds, and pigs.

Type B influenza predominately infects only humans. Type C influenza infects humans and pigs, but is a much rarer cause of infection than either type A or B.

All influenza viruses undergo a process known as "antigenic drift". This refers to random mutations that occur in the RNA genome of the virus. These mutations are a result of errors made during replication of the virus' RNA by an enzyme known as RNA-dependent RNA-polymerase. This enzyme has no "proof-reading" capability like its DNA counterpart. Without proof-reading abilities the enzyme can occasionally substitute incorrect nucleic acids during the viral replication process. Over time these random mutations give rise to new viral strains.

Another process known as "antigenic shift" occurs in type A influenza. Antigenic shift occurs when human and bird strains of influenza A concomitantly infect another host such as a pig. When this happens an influenza RNA "soup" occurs in the cells of the infected pig. This soup causes mixing of the human and bird virus RNA molecules, which can produce entirely new strains of influenza rapidly.

Both antigenic drift and shift produce novel viral strains of influenza. This prevents human antibodies from being affective at stopping subsequent infections. This is the basis behind epidemics and pandemics, which occur when a novel strain spreads rapidly through a population.

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Signs and Symptoms

Influenza produces many non-specific symptoms, which means they can be seen in many other diseases. The most common symptoms include fever, body and muscle aches, rhinorrhea (ie: runny nose), sore throat, non-productive cough, and headache.

The term "stomach flu" is commonly used by people, but is not due to influenza virus. It is uncommon for influenza to cause gastrointestinal symptoms like diarrhea or vomiting.

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Diagnosis

There are a whole boat load of tests aimed at detecting influenza virus. On an outpatient basis rapid diagnostic tests are frequently used, which vary significantly in their ability to detect the virus.

Non-rapid testing such as viral culture, viral polymerase chain reactions, and immunofluorescence are much more sensitive, but require longer periods of time for test results to come back. They are used more frequently in hospital settings.

Nearly every type of test requires swabbing of the back of the patient's nasopharynx (uuuhhggg, gag me!).

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Treatment

Like the old saying goes, "the best offense is sometimes a good defense". This is no less true for influenza. Immunizations can not only prevent disease from developing, but can also help slow the spread of disease through a population because fewer people develop and carry the infection.

Most patients who develop influenza do not need specific treatment. Most cases of flu are self-limited. Therefore, in an otherwise healthy adult, supportive and symptomatic treatments (ie: fluids, fever reducers like acetaminophen) are all that is necessary.

In select patient populations medications may be indicated, but their use depends on the type of influenza, time since onset of symptoms, and the resistance of the virus to the medications. There are two categories of medications used to treat influenza: neuraminidase inhibitors and viral uncoating inhibitors.

Neuraminidase inhibitors include oseltamivir (Tamiflu®) and zanamivir (Relenza®). They inhibit the viral protein neuraminidase, which normally helps newly formed viral particles bud off of infected cells. By inhibiting this process neuraminidase inhibitors decrease the spread of virus from cell to cell, and person to person.

Viral uncoating inhibitors include amantadine and rimantidine. Their mechanism of action is to inhibit a viral protein (M2), which is necessary for the virus to uncoat itself once inside a host cell. Most influenza strains are resistant to these medications, including all strains of influenza B. Therefore their clinically utility is often minimal.

The use of anti-flu medications is highly dependent on the strain of influenza circulating during any given year. Therefore, one year oseltamivir may be the best medication, and the next year amantadine may work best. This is why the Center for Disease Control comes out with yearly flu guidelines.

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Overview

Influenza is an enveloped, single-stranded, segmented, negative-sense RNA virus. There are three types that infect humans. They all undergo genetic drift secondary to mutations during RNA replication. Type A influenza can also undergo antigenic shifts. Both of these mechanisms prevent humans from developing resistance to the virus. Symptoms can range from severe to minimal and often include fever, cold like symptoms, and muscle pain. Treatment is often supportive, but in some cases neuraminidase inhibitors may be effective.

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Related Articles

- Enterobius vermicularis (pinworm)

- Giardia lamblia

- Community acquired pneumonia

- Borrelia burgdorferi

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References and Resources

(1) Le T, Bhushan V, Grimm L. First Aid for the USMLE Step 1. New York: McGraw Hill, 2009.

(2) Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. Seventh Edition. Philadelphia: Elsevier Saunders, 2004.

(3) Gladwin M, Trattler B. Clinical Microbiology Made Ridiculously Simple. Fourth Edition. Miami: Medmaster, Inc., 2007.

(4) "CDC - Seasonal Influenza (Flu)." Centers for Disease Control and Prevention. Web. (http://www.cdc.gov/flu).

(5) Schultz-Cherry S, Jones JC. Influenza vaccines: the good, the bad, and the eggs. Adv Virus Res. 2010;77:63-84.

(6) Brady RC. Influenza. Adolesc Med State Art Rev. 2010 Aug;21(2):236-50, viii.

(7) Dale SE. The role of rapid antigen testing for influenza in the era of molecular diagnostics. Mol Diagn Ther. 2010 Aug 1;14(4):205-14.

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Fever, as medically defined, is any temperature greater than 100.4 F (38 C).
Hemagglutinin refers to the ability of this glycoprotein to cause red blood cells to stick together (aka: agglutinate) in a test tube.
RNA dependent RNA polymerase is an enzyme that allows viruses to convert negative-sense RNA (ie: RNA that does not encode for protein molecules) into positive sense RNA. Positive-sense viral RNA is in essence mRNA, which is the "code" that allows cells to generate proteins. Once RNA-dependent RNA-polymerase converts the RNA to positive sense the virus will use the infected cell's ribosomes to produce viral proteins, which are then packaged into new viral particles that are able to bud off the cell.