respiratory viruses 1 Flashcards
Influenza virus structure
Large, enveloped, negative-stranded RNA viruses (ssRNA). Orthomyxovirus. Has 8 genome segments and each segment has RNA-dependent RNA polymerase proteins PB1, PB2 and PA. The envelope is a lipid bilayer from host cell with viral hemagglutinin and tetrameric neuraminidase. M1 protein under lipid bilayer and M2 protein forms ion channel
enterovirus D68 structure
Small,non-enveloped, positive-stranded RNA viruses
Influenza: Clinical Characteristics
headache, fever (38-41 over 1-5 days), sweating, chills, malaise, anorexia, sore throat, nasal congestion, myalgias, dry cough, pneumonia
complications of influenza
influenza pneumonia, bacterial pneumonia, and rarely encephalopathy, myositis, myocarditis, pericarditis, transverse myelitis, reyes syndrome, guillan-barre syndrome
risk factors for influenza
> 65 years, chronic diseases (pulmonary, heart, diabetes), pregnancy, immunosuppression, long term aspirin therapy in kids
Primary influenza infection pathogenesis
incubation period 24-48 hrs. Local virus replication in respiratory epithelium (no viremia) > Macrophage and lymphocyte infiltration into lung > Innate immune responses interferon and cytokines cause fever, myalgia etc > Direct virus damage and acquired immune responses kill infected epithelial cells and/or neutralize virus particles> Elicits antibodies and influenza-specific T cells, locally and systemically > Clearance of virus and dead cells from respiratory tract
Length of influenza infection and immunity
Illness can last 5 days to 2 weeks. Immunity to re-infection is mediated by type-specific antibody in respiratory secretions, which is antibodies to epitopes on viral HA or NA glycoproteins. If levels of IgA in respiratory tract are high enough that person will be protected from that strain of virus in future. Partially immune people may get mild sx but still shed enough virus to infect others.
Hemagglutinin functions
95% of spikes on influenza. 1. Binds to N-acetyl neuraminic acid on host cell surface. 2. HA cleavage by host cell proteolytic enzyme inot HA1 and HA2 required for viral infectivity. 3. HA2 undergoes conformational change at low pH in endosome following endocytosis. This is required for fusion of viral envelope with host cell membranes.
HA structure in highly pathogenic strains of influenza A
have a longer series of basic amino acid sequences at the cleavage site in HA0.
Neuraminidase functions
5% of influenza spikes. 1. cleaves N-acetyl neuraminic acid from host cell membrane (receptor destroying enzyme). 2. removes receptor from host cell membranes as they move through the Golgi so that newly budded virions do not stick to the infected cells, but can detach and infect other cells.
Which drugs act on neuraminidase
zanamivir and oseltamivir inhibit NA enzyme activity, thus blocking the removal of receptors from infected cell surface and preventing release of new virions from infected cell. This prevents the spread of influenza A and B. Shortens sxs
influenza matrix protein, M, functions
Three types, M1, M2, M3. during virus budding at the plasma membranes, M protein binds nucleocapsids containing each of the 8 genome segments to the viral envelope. M2 is ion pump that raises pH in endosomes of infected cells. Since acidic pH is required for release of viral genes into host cytoplasm via HA2, M2 prevents fusion of intracellular membranes and cytopathology
Which drugs act on Matrix proteins
Amantadine and rimantadine target M2 (anti-influenza A only)
influenza nucelocapsid protein functions
protects viral RNA from degradation. Differs antigenically btw influenza A, B and C
Influenza non-structural proteins functions
NS1 is an antagonist of the host interferon response. Also virus assembly/ replication and transporting nucleocapsids in and out of nucleus.
