Influenza causes

Influenza Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Influenza from other Diseases
Epidemiology and Demographics
Risk Factors
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
Chest X Ray
Other Diagnostic Studies
Treatment
Medical Therapy
Primary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Influenza causes On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Influenza causes All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Influenza causes
CDC on Influenza causes
Influenza causes in the news
Blogs on Influenza causes
Directions to Hospitals Treating Influenza
Risk calculators and risk factors for Influenza causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Taxonomy

• There are three types of influenza viruses: A, B and C.
• Human influenza A and B viruses are responsible for causing seasonal epidemics of the disease almost every winter in the United States.
• The emergence of a new and very different influenza virus to infect people can cause an influenza pandemic.
• Influenza type C infections cause a mild respiratory illness and are not thought to cause epidemics.
• The international naming convention for influenza viruses uses the following components to name the virus:

• The antigenic type (e.g., A, B, C)
• The host of origin (e.g., swine, equine, chicken, etc. For human-origin viruses, no host of origin designation is given.)
• Geographical origin (e.g., Denver, Taiwan, etc.)
• Strain number (e.g., 15, 7, etc.)
• Year of isolation (e.g., 57, 2009, etc.)
• For influenza A viruses, the hemagglutinin and neuraminidase antigen description in parentheses (e.g., (H1N1), (H5N1)

Influenza A

• Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: the hemagglutinin (H) and the neuraminidase (N). There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes. (H1 through H18 and N1 through N11 respectively.)
• Influenza A viruses can be further broken down into different strains. Current subtypes of influenza A viruses found in people are influenza A (H1N1) and influenza A (H3N2) viruses. In the spring of 2009, a new influenza A (H1N1) virus (CDC 2009 H1N1 Flu website) emerged to cause illness in people. This virus was very different from the human influenza A (H1N1) viruses circulating at that time. The new virus caused the first influenza pandemic in more than 40 years. That virus (often called “2009 H1N1”) has now replaced the H1N1 virus that was previously circulating in humans.

Influenza B

• Influenza B viruses are not divided into subtypes, but can be further broken down into lineages and strains.
• Currently circulating influenza B viruses belong to one of two lineages: B/Yamagata and B/Victoria.

Biology

Genetics

"The physical structure of all influenza A viruses is similar. The virions or virus particles are enveloped and can be either spherical or filamentous in form. In clinical isolates that have undergone limited passages in eggs or tissue culture, there are more filamentous than spherical particles, whereas passaged laboratory strains consist mainly of spherical virions."

The Influenza A virus genome is contained on eight single (non-paired) RNA strands that code for eleven proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2). The segmented nature of the genome allows for the exchange of entire genes between different viral strains during cellular cohabitation. The eight RNA segments are:

• HA encodes hemagglutinin (about 500 molecules of hemagglutinin are needed to make one virion) "The extent of infection into host organism is determined by HA. Influenza viruses bud from the apical surface of polarized epithelial cells (e.g. bronchial epithelial cells) into lumen of lungs and are therefore usually pneumotropic. The reason is that HA is cleaved by tryptase clara which is restricted to lungs. However HAs of H5 and H7 pantropic avian viruses subtypes can be cleaved by furin and subtilisin-type enzymes, allowing the virus to grow in other organs than lungs."
• NA encodes neuraminidase (about 100 molecules of neuraminidase are needed to make one virion).
• NP encodes nucleoprotein.
• M encodes two matrix proteins (the M1 and the M2) by using different reading frames from the same RNA segment (about 3000 matrix protein molecules are needed to make one virion).
• NS encodes two distinct non-structural proteins (NS1 and NEP) by using different reading frames from the same RNA segment.
• PA encodes an RNA polymerase.
• PB1 encodes an RNA polymerase and PB1-F2 protein (induces apoptosis) by using different reading frames from the same RNA segment.
• PB2 encodes an RNA polymerase.

The genome segments have common terminal sequences, and the ends of the RNA strands are partially complementary, allowing them to bond to each other by hydrogen bonds. After transcription from negative-sense to positive-sense RNA the +RNA strands get the cellular 5' cap added by cap snatching, which involves the viral protein NS1 binding to the cellular pre-mRNAs. The cap is then cleaved from the cellular pre-mRNA using a second viral protein, PB2. The short oligo cap is then added to the influenza +RNA strands, allowing its processing as messenger RNA by ribosomes. The +RNA strands also serve for synthesis of -RNA strands for new virions.

The RNA synthesis and its assembly with the nucleoprotein takes place in the cell nucleus, the synthesis of proteins takes place in the cytoplasm. The assembled virion cores leave the nucleus and migrate towards the cell membrane, with patches of viral transmembrane proteins (hemagglutinin, neuraminidase and M2 proteins) and an underlying layer of the M1 protein, and bud through these patches, releasing finished enveloped viruses into the extracellular fluid.

Natural Reservoir

Canine

Different hemagglutinin and neuraminidase subtypes and the species in which they have been detected

Species	Hemagglutinin Subtypes	Neuraminidase Subtypes
Humans	H1, H2, H3, H5, H6, H7, H9, H10	N1, N2, N6, N7, N8, N9
Poultry	H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16	N1, N2, N3, N4, N5, N6, N7, N8, N9
Pigs	H1, H2, H3, H4, H5, H9	N1, N2
Bats	H17, H18	N10, N11
Adapted from CDC