Transcript Influenza
Influenza Sara Finestone April 8, 2010 The influenza virus causes 3-5 million cases of severe illness and up to 500,000 deaths annually Pandemics cause millions of deaths 1918 Spanish flu 1918-1920 > 40 million H1N1 Asian flu 1957-1958 2 million H2N2 Hong Kong flu 1968-1969 1 million H3N3 Swine flu 2009-present 15,000-20,000 H1N1 One study predicted 96% of deaths in a future pandemic would be in developing countries! One study predicted 96% of deaths in a future pandemic would be in developing countries! Anti-viral medications remain too expensive One study predicted 96% of deaths in a future pandemic would be in developing countries! Anti-viral medications remain too expensive World production of vaccines too low to provide to all countries One study predicted 96% of deaths in a future pandemic would be in developing countries! Anti-viral medications remain too expensive World production of vaccines too low to provide to all countries Weak public health infrastructure Disease burden is much higher in developing countries Limited access to healthcare Malnutrition Immunosuppression Parasitic diseases Increased risk of severe complications Infant pneumonia Symptoms similar to common cold Fever Cough Nasal Congestion Aches Fatigue Vomiting Family Orthomyxoviridae Influenza A Thogotovirus Isavirus Influenza B Influenza C The Virion Glycoproteins Hemagglutinin (HA) Neuraminidase (NA) The Virion Glycoproteins Hemagglutinin (HA) Neuraminidase (NA) Central Core 7-8 pieces of single, negative strand segmented RNA Virus is transmitted by: Airborne- aerosols containing virus Hand-eye/nose/mouth The viral Hemagglutinin (HA) protein mediates viral entry. The viral Hemagglutinin (HA) protein mediates viral entry. HA binds to sialic acid receptors on epithelial cells of nose, throat, and lungs HA determines what species virus infects and where in the respiratory tract virus binds Enters cell through endocytosis Acidic environment of endosome permits: • Viral envelope to fuse with vacuole’s membrane • Protons to enter through M2 ion channel, acidifying core of virus Core dissembles, viral RNA and proteins are released, and viral RNA Polymerase makes mRNAs and copies genome New viral proteins are transcribed and viral RNA, RNA-dependent RNA polymerase and other proteins are assembled into new virion Neuraminidase cleaves host sialic acid residue to detach virion from host cell Influenza is highly variable! RNA-dependent RNA polymerase makes about 1 error per replication 7-8 segments of RNA allow for reassortment This variability leads to antigenic drift and explains why there are so many strains of the flu. Treatments target proteins unique to virus M2 protein inhibitors Adamantanes (Amantadine, rimantadine) Neuraminidase inhibitors Oseltamivir (Tamiflu) Zanamivir (Relenza) Vaccines recommended for high risk groups Inactivated virus or avirulent live virus Contain two influenza A subtypes and one influenza B subtype Differences between strains and vaccines and circulating strains limit vaccine effectiveness Produced 6-8 months ahead of flu season References Tosh, P.K., R.M. Jacobson, & G. Poland. “From surveillance through production to protection.” Mayo Clinic Preceedings, 85 (2010): 257-273. Oshitani, H., T. Kamigaki, and A. Suzuki "Major Issues and Challenges of Influenza Pandemic Preparedness in Developing Countries." Emerging Infectious Diseases 14.6 (2008): 875-880. Simonsen, Lone. "Influenza-related Morbidity and Mortality Among Children in Developed and Developing Countries." International Congress Series 1219 (2001): 13-19 De Clercq, Erik. "Antiviral Agents Active Against Influenza a Viruses." National Reviews Drug Discovery 5 (2006): 1015-1025. Bouvier, Nicole M., and Peter Palese "The Biology of Influenza Viruses." Vaccine 26.4 (2008): D49-D53. Karlsson Hedestam, Gunilla B. et al "The Challenges of Eliciting Neutralizing Antibodies to HIV-1 and to Influenza Virus." Nature Reviews Microbiology 6 (2008): 143-155. Mitrasinovic, Petar M. Global View of the Fight Against Influenza. New York: Nova Science Publishers, Inc., 2009. Print. Ryan, Jeffrey R. Pandemic Influenza: Emergency Planning and Community Preparedness. Florida: CRC P, 2009. Print. WHO, World Health Organization. <http://www.who.int/en/>. CDC, Centers for Disease Control. <http://cdc.gov>.