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 > 40 millionH1N1 Asian flu millionH2N2 Hong Kong flu millionH3N3 Swine flu2009-present15,000-20,000H1N1

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 Influenza B Influenza C Isavirus Thogotovirus

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.

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): Oshitani, H., T. Kamigaki, and A. Suzuki "Major Issues and Challenges of Influenza Pandemic Preparedness in Developing Countries." Emerging Infectious Diseases 14.6 (2008): Simonsen, Lone. "Influenza-related Morbidity and Mortality Among Children in Developed and Developing Countries." International Congress Series 1219 (2001): De Clercq, Erik. "Antiviral Agents Active Against Influenza a Viruses." National Reviews Drug Discovery 5 (2006): 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): Mitrasinovic, Petar M. Global View of the Fight Against Influenza. New York: Nova Science Publishers, Inc., Print. Ryan, Jeffrey R. Pandemic Influenza: Emergency Planning and Community Preparedness. Florida: CRC P, Print. WHO, World Health Organization.. CDC, Centers for Disease Control..