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RS Microbiology

Respiratory System Microbiology - Virology of the Influenza Virus

Influenza virus belongs to: the Orthomyxoviridae family
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
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
Antigenic shifts are associated with influenza pandemics with more severe symptoms than those accompanying influenza epidemics
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
A new more virulent strain develops by antigen drifts every: 3-5 years
Antigenic shifts produce a more virulent strain every: 7-10 years
What other virus has segmented genome? Rotavirus
Influenza type A and B have how many segments? 8
Influenza type C has how many segments? 7
Human, avian, swine and horse flu are caused by Type A
Type B and C affect: Humans
Type A is associated with BOTH antigenic shifts and drifts
Type B is associated with antigenic drifts ONLY
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
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
The most antigenic glycoprotein is The H protein
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
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
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
Each RNA segment encodes one specific viral protein. Segment 4 and 6 encode: Segment 4 encodes hemagglutinin Segment 6 encodes neuraminidase
High frequency of antigenic drifts and shifts (reassortment) is a characteristic of Orthomyxoviruses
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
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
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
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
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
Symptoms of Influenza: Fever, headache, myalgia, cough, rhinitis, ocular symptoms such as conjunctivitis
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
Diagnosis of influenza virus: Mainly based on clinical presentation
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
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)
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
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
Created by: Ulaisl