Respiratory System Microbiology - Virology of the Influenza Virus
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| Influenza virus belongs to: | the Orthomyxoviridae family
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| Characteristics of the Influenza Virus: | 1) Enveloped virus
2) Helical capsid
3) 3 types of the virus: A,B,C (least severe)
4) continuous variation in its genome
5) Segmented genome
6) Hemagglutinin and the neuraminidase
7) Other structural proteins include: M1, M2 and NEP proteins
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| Continuous variation in the Influenza virus genome is characterized by: | 1) RNA dependent RNA polymerase lacks proof reading - point mutations every 2500-10000 bases
2) Antigenic shift (aka re-assortment) when a cell becomes infected with more than one species of the virus creating new combinations of viral gene segments
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| Antigenic shifts are associated with | influenza pandemics with more severe
symptoms than those accompanying influenza epidemics
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| Why do antigenic shifts cause pandemics with severe symptoms, whereas antigenic drifts cause epidemics with less severe symptoms? | Point mutation causes minimal change in the structure,antibody still can bind the virus but with less affinity
Production of a more virulent virus, affinity for the pre-formed
antibodies drops from 95% to 20-30% approximately
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| A new more virulent strain develops by antigen drifts every: | 3-5 years
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| Antigenic shifts produce a more virulent strain every: | 7-10 years
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| What other virus has segmented genome? | Rotavirus
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| Influenza type A and B have how many segments? | 8
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| Influenza type C has how many segments? | 7
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| Human, avian, swine and horse flu are caused by | Type A
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| Type B and C affect: | Humans
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| Type A is associated with | BOTH antigenic shifts and drifts
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| Type B is associated with | antigenic drifts ONLY
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| Classes of drugs used for influenza: | Neuraminidase inhibitors for A/B since it inhibits NA protein
The second class of drugs is amantadine and rimantadine. These drugs affect the un-coating step by binding to the M2 protein which is present in type A only
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| Characteristics of H proteins: | 15 H proteins (H1-H15,strain-specific)
Most important in humans are H1, H2 and H3
The name hemagglutinin is derived from the ability of this protein to agglutinate erythrocytes
The primary role of H protein is attachment to target cell receptors
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| The most antigenic glycoprotein is | The H protein
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| Characteristics of N proteins: | 12 or 13 types
Most important are 1, 2
Binding between N-acetylneuraminic acid part of the host cell’s receptor and virus is cleaved by the neuraminidase in order to free the virus to infect nearby cells
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| N proteins also have a role in: | The fusion of the viral envelope to the membrane of the host cells
Inactivation of mucoprotein receptor in respiratory secretions
Facilitating the release of viral particles from infected cells during budding and prevention of virion aggregation
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| Nomenclature of Influenza virus: | Type ( A,B,C )
Host origin (human,avian , swine , horse – when the host is human, not mentioned)
Geographical origin
Description of the S-antigen
Strain no.
Year of isolation
Antigenic designation of H and N
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| Each RNA segment encodes one specific viral protein. Segment 4 and 6 encode: | Segment 4 encodes hemagglutinin
Segment 6 encodes neuraminidase
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| High frequency of antigenic drifts and shifts (reassortment) is a characteristic of | Orthomyxoviruses
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| The avian influenza A subtype H5N1 | First documented infection of human by avian influenza in 1997 Hong Kong
No mixture of human/avian genome segments
Global pandemic
Infection acquired through birds
An infected human is not contagious
Other pandemics-mixture of human and avian genome
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| Pathogenesis of Influenza: | Primary source of infection is droplets or aerosols, also fomites
Influenza can cause upper and lower RTIs, most commonly upper
The infection spreads to reach the lower respiratory tract
Bacterial super-infection
Desquamation of cells
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| You might recover from influenza after a few days of infection, however; the cough may persist for weeks since | The cilia need 8-12 weeks to return to their original shape
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| Some consequences of influenza : | 1ry viral pneumonia by the influenza virus (in lower respiratory tract)
2ry bacterial super-infection
Muscles and CNS might be involved
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| Immunity of Influenza: | Intracellular viruses presented by MHC1 molecules to be detected by CD8 + that release perforins and granzymes
Extracellular antigens engulfed by macrophages, represented by MHC 2 molecules and detected by CD4
TH2 cells activate B cells to release Abs
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| Symptoms of Influenza: | Fever, headache, myalgia, cough, rhinitis, ocular symptoms such as conjunctivitis
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| Complications of influenza virus : | Croup
1ry viral pneumonia
2ry bacterial infection (strep. pneumoniae , Staph. aureus and Haemophilus) -otitis media/sinusitis
Myositis, cardiac,CNS,PNS, & liver symptoms
Reyes Syndrome - fat deposition in liver, brain edema, vomiting, lethargy, coma
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| Diagnosis of influenza virus: | Mainly based on clinical presentation
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| Prevention and treatment: | Vaccines and antiviral drugs are available
Amantadine and Rimantadine: Block the un-coating step by inhibiting the M2 protein which is present in influenza A
Oseltamivir (Tamiflu) and Zanamivir
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| There are two forms of influenza vaccine: | An injected form: Widely used globally, given IM in the shoulder
An intranasal form
An influenza vaccine consists of 3 types of antigens (2 from influenza A and one from influenza B)
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| Characteristics of the injected form of vaccination: | 1) Inactivated (killed) virus vaccine
2) Made by growing the most three virulent strains, then addition of formalin
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| Characteristics of the intranasal form of vaccination: | Live attenuated vaccine
Contraindicated in immunocompromised
Eggs and cell lines- used as incubators
Gene segments of the most three virulent virus strains, re-assortment is done to incorporate them
In incubators,temperature lowered to 23 degrees
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