Influenza Flashcards

Question

Spanish flu pandemic 1918

Answer 1

- young and old died but also a spike in deaths of young adults is what made the 1918 flu unusual - one of the greatest pandemics, infected > 500 million people, about 50 million died - people betweeen 15 and 34 years old most differentially affected - death rate 20x higher than previous years for people WITHOUT a bacterial superinfection (which is what the avian flus are now doing which is concerning) - approximately half of soldiers who died in WWI died of flu - 2.5% mortality rate compared to normal .1% rate **highly virulent, often killed people directly without bacterial superinfection Death carts in 1918 in philadelphia

Answer 2

Molecular archeology! Pathological specimen (circa 1918) because the army doesnt throw anything out so you could find people who died back then and get their preserved lung tissues —> gene sequencing and PCR to amplify flu genes —> gene reconstructions —> reverse genetics—> phenotypic characteriziation in tissue cultures and animal models - Jeff Taubenberger After seeing this molecular archeologists Johan Hilton excavated a mass grave in Alaskas Seward Peninsula where in 1918 72/80 ppl died from flu in 6 day period—> mass grave preserved by permafrost - found an obese woman in her mid20s when she died of influenza, whose tissues were rather well preserved

Answer 3

Far more virulent in animals Triggers aberrant innate immune responses: - less IFN production, so likely more virus replication - much higher levels of cytokines - leads to vascular permeability, pulmonary edema (induces cytokine storm leading to pulmonary edema and respiratory fluid )

Answer 4

Expensive guess as to what the seasonal flu is going to look like a year later Decisions about what strains to include are made in Jan/feb Virus selection—> production begins—> FDA testing licensure—> filling and packaging—> product release—> vaccine begins oct-nov (immunity develops 2 weeks after vaccination All flu vaccines contain the HA proteins from 1 or 2 influenza B, one H1N1 and one H3N2 virus, these change on a yearly basis WHO has a worldwide network of inelunza surveillance labs, in Jan/Feb of each year, decision is made about the three viruses that will compose the influenza vaccine in the coming winter, takes 6 mo to make the vaccine

Answer 5

All contain the HA proteins from 3 or 4 influenza strains, these can change each year Three types of vaccines that can deliver these HA proteins Inactivated vaccine: produced in eggs (flu is grown in embryonated chicken eggs, partially purified and inactivated) - partially purified, inactivated, most common - delivered IM and is the oldest and most common Life ATtenuated (FluMist) - produced in eggs, virus is adapted to only grow at lower temperatures, and then is engineered to express whatever HA proteins are recommended for the yearly vaccine - virus replicates in the nose and induces good immunity - produced in eggs - squirt this mix of viruses up your nose and because it is adapted to grow at lower temperatures it wont really spread - dont give to young, old, pregnant, immunosuppressed Subunit Recombinant (FluBlok) - licensed in 2013, new, relevant HA proteins are produced in insect cells, so you use this vaccine for people with egg allergies

Answer 6

Seasonal flue vaccine, influenza B, A H1 and A H3 viruses Increasing number of vaccines include four viruses (two influenza Bs)

Answer 7

Recommended for all persons > 6 months Children 6 mos - 8 yrs: two doses 4 weeks apart High dose shot used for persons > 65 yo Life attenuated preferred for children 2 -8 yrs Life attenuated shouldn’t be used for - < 2yo, > 49 yo - pregnant women - immunocompromised - persons with history of egg allergy - children 2 - 4 with asthma Persons with egg allergies: - can give standard vaccine to people who have mild reactions to egg products - can use recombinant flu vaccine **WHEN IN DOUBT—> inactivated vaccine can be given to anyone save for those with significant egg allergies** Differences in use Live attenuated: small pox, yellow fever, mumps, measles, rubella, flu mist, rotavirus, chickenpox, Sabin polio Killed/inactivated: influenza, hep A, Salk polio, rabies Subunit: HepB, HPV

Answer 8

M2 ion channel is the target for amantadine - “uncoating” - M2 ion channel inhibitors - amantadine - when virus enters the cytoplasm, capsid falls apart buut then a few hours later same RNA segments and NP proteins assemble to form new capsids - M2 protein is a proton channel and tells the NP protein to dissasemble and assemble - when virus enters an endoscope, not only is HA triggered to cause fusion,, but protons flow through the M2 Channel into the viral core—> acid bath to the viral capsid and triggers it to dissociate so that nuclear transport can then occur - newly synthesized NP protein has never seen acid pH so it is ‘different’ than NP that enters to the cell - acid pH is the switch that regulates viral assembly and disassembly, causes a conformational change in HA NB influenza is unique in that it replicates in the nucleus but normally RNA viruses replicate in the cytoplasm and DNA in the nucleus Amantadine (symmetries) and Rimantidine (flumadine) = small molecule inhibitors of M2 protein, bind to channel and prevent acidification of viral core—> prevent virus disassembly and prevent infection, but most drugs resistant to this now

Answer 9

Oseltamivir and related molecules are both NA inhibitors Can ameliorate symptoms but dont stop infection By inactivating NA they limit virus spread - virus particles emerging from an infected cell bind to the host cell sialic acid, and cannot ‘cleave’ themselves off of the receptor so spread to adjoining cells is inhibited

Answer 10

M2 ion channel inhibitors amantadine (symmetrel), flue type A, used for treatment and prevention, treatment age > 1 yr Rimantidine (flumadine), flu type A, used for treatment and prevention, treatment in adults Neuraminidase inhibitors - block virus release from cell surface - zanamivir (relenza) treat A/B, used for treatment, > 7 yo, inhalation - oseltamivir (Tamiflu), treat A/B > 1 yr for brevention and treatment, oral Most viruses circulating are resistant to amantadine, drugs that target NA are usually effective in limiting virus spread

Answer 11

B becuase this is antigenic drift and leads to epidemics A. .presence of such reservoirs is why flu A but not flu B or c can cause pandemics C. Makes reassortment possible D. Without this you cant have reassortment E. For viruses to coninfect a cell, they have to recognize sialic acid linkages on that cell

Answer 12

A. Influenza pneumonia B. Other viral pneumonia C. Rhinotracheitis from influenza D. Bacterial pneumonia D!!

Answer 13

B!! A. Target of neutralizing AB C. Tamiflu- prevent virus release D. M2 amantadine prevent virus uncoating by preventing protons from flowing through M2 ion channel in the viral membrane following endocytosis