Myxoviruses Tutorial Materials

Myxoviruses Myxoviridae Myxo Mucous Beyond, Beside Correct, Right Paramyxoviruses SS RNA(-) SS RNA(-) Size Site of Nucleocapsid Formation Genome Orthomyxoviruses 120-250 nm (large) Cytoplasm Nonsegmented 80-120nm (small) Nucleuos Segmented Genetic Shift - + H & N Separately - + Myxoviruses Respiratory viruses  transmission through droplet dispersion Orthomyxoviridae INFLUENZA o severe respiratory disease o 20-50 million respiratory illnesses each year in the U.S.  30 million visits to physicians, 200,000 hospitalizations  20,000 deaths o new influenza virus strains associated with severe pandemics and high mortality. History of Flu in world 1918 H1N1 “Spanish Influenza” 20-40 million deaths 1957 H2N2 “Asian Flu” 1-2 million deaths 1968 H3N2 “Hong Kong Flu” 700,000 deaths 1977 H1N1 Re-emergence No pandemic 2009 H1N1 “Swine Flu Mild Pandemic Classification 1) Influenza A 2) Influenza B 3) Influenza C type A, B, C : RNP, M1 protein sub-types: HA or NA protein According to antigenicity of HA and NA, influenza A virus is divided into subtypes such as HnNm( H1N2) : There are 18 known HA subtypes and 11 known NA subtypes. Types of Influenza Viruses Type A      Humans Swine Birds Horses Seals Type B  Humans Type C Type A undergoes antigenic shift and drift. Type B undergoes antigenic drift only and type C is relatively stable  Humans  Swine Human influenza virus Influenza A/Bangkok/1/79(H3N2) Influenza A/Singapore/1/57(H2N2) Influenza B/Ann Arbor/1/86 Influenza type Year of isolation Hemagglutinin subtype A/Sydney/5/97 (H3N2) Geographic source Isolate number Neuraminidase subtype Morphology • Spherical/ovoid • 80-120nm diameter. • Single-stranded ,RNA negative sense. • genome replicates in nucleus. • The inner side of the envelope is lined by the matrix protein (M1). • The outer surface consists of a lipid envelope which project prominent glycoprotein spikes of 3 types, the haemagglutinin(HA), neuraminidase(NA) and Ion channel (M2). Structure of the influenza Hemagglutinin (HA)  The HA is a trimeric rod-shaped molecule  Can agglutinate red blood cells - hence the nomenclature (hemagglutinates human RBCs)  Attachment protein, bind to sialic acid cell receptors  promotes fusion of envelope to cell membrane  It induce the protective neutralizing antibody response Neuraminidase (NA) • Enzyme that uses neuraminic (sialic) acid as a substrate • Important in releasing mature virus from infected cells and cleaning the environment (e.g., mucus and cell surfaces) of sialic acid receptors to allow for virus spread. • Structure: Box-shaped tetramer with stalk that anchors it to the membrane • Function: Cleaves off sialic acid molecules from the surface of cells thereby preventing infected cells from “recapturing” budding virus molecules. Replication of influenza A viruses ***The nucleus is where viral RNA replication occurs. Influenza type A High Risk for Complications  People over 50  infants  Chronic lung disease, asthma  Chronic heart disease  Metabolic diseases, e.g. diabetes Epidemiology  Reservoir  Human, animals  Transmission  Respiratory airborne  Temporal pattern  seasonal  Chronic renal disease  Immunosuppression  Pregnancy  Communicability  Maximum 1-2 days before to 4-5 days after onset flu viruses change Mutation: Drift Reassortment: Shift flu viruses change SYMPTOMS • • • • • • FEVER HEADACHE MYALGIA COUGH RHINITIS OCULAR SYMPTOMS Viremia rarely documented Viral shedding in respiratory secretions for 5-10 days INFLUENZA COMPLICATIONS 1. CROUP 2. PRIMARY PNEUMONIA 3. SECONDARY BACTERIAL INFECTION Streptococcus pneumoniae Staphlyococcus aureus Hemophilus influenza 4. liver and CNS Reye syndrome 5. peripheral nervous system Guillian-Barré syndrome – (is a rare disorder in which body's immune system attacks the nerves) DIAGNOSIS • ISOLATION – Nasopharyngeal SWAB – Cell culture OR with EGGS • SEROLOGY • RAPID TESTS (Molecular ) • provisional - clinical picture + outbreak Antiinfluenza medications Two Classes of Medications Available 1) Adamantanes (Preventing fusion of the virus & host cell membranes)  Amantadine  Rimantadine 2) Neuraminidase inhibitors  Oseltamivir (Tamiflu)  Zanamivir((Relenza) Prevention • The proven method for preventing influenza is a yearly vaccination approximately 2 weeks before the “flu season” begins. • The influenza vaccine is trivalent, it consists of three strains( 2 influenza A virus and 1 influenza B virus). • Since the influenza virus is subject to genetic mutations with the HA and NA proteins, new vaccines that consist of different influenza strains need to be developed each year. living and nonliving Influenza Vaccines Replicating Vaccines Antigens are replicated in host Non-Replicating Vaccines Antigens are manufactured outside the host LAIV TIV Live-attenuated influenza vaccine Trivalent Inactivated vaccine Intranasal CAIV-T (Cold-adapted influenza vaccines trivalent) Live attenuated Replication restricted to the cooler upper airways Intramuscular -Whole virus -Split vaccine -Subunit vaccine -Single protein -Virosome -virus-like particles