Influenza Viruses Flashcards

Question

Wha tis the mRNA synthesis and replication of virion RNA?

Answer 1

After the viral RNPs enter the nucleus, mRNA synthesis begins. Cap-snatching process * Viral PB2 protein binds to the cap structure on the cellular mRNA * Viral PB1 cleaves the RNA 10-13 nt from its 5' end * PB1 uses cap as a primer from copying genome RNA into viral mRNA *

Answer 2

**“Stuttering” Transcription** * Short stretch of poly(U) at end of genomic RNA * Viral RNA polymerase pauses and **“stutters”** at poly(U) sequence * Multiple read-throughs and addition of complementary A residues * Allows for export out of the nucleus into the cytoplasm for translation

Answer 3

**NS1** is most abundant protein in infected cells * Interferes with polyadenylation of cellular mRNAs * Prevents nuclear export of cellular mRNAs **PB1 and PB2** degrade cellular pre-mRNAs

Answer 4

* Transcription generates complete set of 8 viral mRNAs * Six mRNAs are exported directly to the cytoplasm * Two influenza A mRNAs contain splicing sequences recognizable by cellular splicing machinery and undergo alternative splicing Unspliced RNAs create M1 and NS1 Spliced RNAs create M2 and NS2 (less abundant)

Answer 5

Genome replication begins when newly synthesized NP protein enters the nucleus * Replication of genome requires **no** primer * PB1 copies genomic RNA into complementary (+) strand that is then coated with NP * A**ntigenome** RNA copied into genomic RNA by same mechanism

Answer 6

The NS1 protein also suppresses a variety of host cell antiviral response pathways * Inhibits RIG-I (triggers release of type I IFN) * Inhibits **double stranded RNA-dependent protein kinase (PKR)** * Inhibits 2’,5’-oligo(A) synthetase/Ribonuclease L PB1-F2 may contribute in suppression of the host immune response * Localizes to mitochondria and induces apoptosis in host immune cells

Answer 7

* Capped mRNAs exported from nucleus are translated by ribosomes in the cytoplasm * H, N, and M2 are folded and glycoylated and transported to the trans-Golgi network and cell surface where assembly takes place * One copy of each genome segment is packaged into the virion.

Answer 8

Virions are released by budding * The viral neuraminidase (NA) proteins cleaves the sialic acid on host cells to prevent clumping of viral particles at the host surface. * Zamanivir (sold as Relenza) and oseltamivir phosphate (sold as Tamiflu) inhibit the function of NA.

Answer 9

* Mutations are common during viral replication. * Viral RNA dependent RNA polymerase lacks proofreading and correction ability. * Two processes, antigenic drift and antigenic shift, mediate genetic variation that causes new strains of influenza to appear.

Answer 10

* Small change in HA and/or NA genes * Selective pressure from immune system * Cause of yearly epidemics * Reason for yearly reformulation of flu vaccine

Answer 11

**Reassortments** between human and bird flu viruses resulting in novel strain * Only occurs with influenza A viruses Responsible for pandemic strains * No antibodies against new strain * Unusally high number of cases and deaths

Answer 12

* Close association of humans with animals and birds * Influenza A is constantly circulatin gin birds, pigs, and horses

Answer 13

* Aerosol spread of influenza virus is dependent upon humidity and temperature * The virus was best transmitted at low humidity and colder temperatures * Supoorting evidence shows that weather conditions play a role in influenza virus transmission

Answer 14

Killed more people in 25 weeks than AIDS killed in 25 years Killed more people in a year than the plagues of the Middle Ages killed in a century Estimated deaths: 20 to 50 million, including 675,000 Americans In NYC, 21,000 children were orphaned by influenza. 7 times as many people died of the 1918 Spanish Flu than in WWI. True estimates will never be known.

Answer 15

* It killed 20- to 40-year old adults * It killed quickly (2-3days) * Those infected suffered from hemorrhagic symptoms

Answer 16

* Johan Hultin exhumed bodies of flu victims buried in frozen ground at Brevig Mission, Alaska. * Removed frozen lung tissues and provided them to Jeffrey Taubenberger (Armed Forces Institute of Pathology in Washington, DC), who sequenced the viral genome of the 1918 strain. * 1918 was an avian—not swine—strain.

Answer 17

* Terrence Tumpey, CDC researcher * Reverse genetics * Work done in an enhanced BSL-3 laboratory

Answer 18

* Infected macaques with the reconstructed 1918 influenza virus * Carried out experiments in a BSL-4 laboratory * Macaques died of SIRS (cytokine storm)

Answer 19

* 70,000 Americans died * Asian flu first identified in northern China (February 1957) and spread to the United States by June 1957 * Vaccine was made and available by August 1957.

Answer 20

* First detected in Hong Kong during early months of 1968 * Reached the United States by September 1968 * Deaths in the United States peaked in December 1968–January 1969 (mostly elderly) * Mildest pandemic in the century, killing only 33,800 people in the United States

Answer 21

* February 1976: Cadets at Fort Dix, NJ came down with the flu; one private died. * CDC investigated the outbreak. * 4 out of 19 throat washings tested positive for H1N1 influenza A (at the time believed to be a “swine” flu closely related to the 1918 Spanish flu virus). * 150 million doses of vaccine were prepared in the United States. * 46 million doses were administered within a few months. * Vaccine was fast-tracked. * Congress passed a liability protection bill to protect manufacturers of the vaccine. * Early problems of the vaccine: * Guillain-Barré syndrome (532 people within 10 weeks) * 32 deaths * Vaccine campaign was suspended in the late fall of 1976. * U. S. government paid more than $90 million on claims cases.

Answer 22

May 1977: Influenza A H1N1 isolated in northern China Primarily children and younger adults became ill. This strain was similar to the 1957 strain. Individuals born before 1957 would have no cross-reacting/partial immunity toward the virus.

Answer 23

May 1997: 3-year-old boy in Hong Kong died. Influenza A isolated from the boy but the H subtype could not be identified. Later confirmed to be H5 H5 not known to infect humans before (subtype isolated from birds only) The “jump” of an avian strain directly to humans had never happened before. The same H5N1 strain was killing chickens.

Answer 24

Veterinary authorities slaughtered chickens to prevent the spread of H5N1 to chickens and people.

Answer 25

Only 18 human cases in 1997 33% fatality rate 1918 flu was about 4% fatal in the United States. It is possible that a single insertion (mutation) could enable the virus to spread much more efficiently to the brain and heart. The most important control measures are: rapid culling of infected or exposed bird and proper disposal of carcasses quarantining and rigorous disinfection of farms Continual surveillance is key 60 individuals infected with H7N9 “bird flu” in China 2013

Answer 26

* Contrary to what many experts expected, the first pandemic of the 21st century started in North America and not in Southeast Asia. * More than 75% of individuals infected were younger than 30 years of age. * U.S. conservative estimates: H1N1 flu deaths ranged from 7,500 to 12,000 * Seroprevalence studies: Older people had strong antibody reactions toward H1N1 than younger people, suggesting they had some cross-reacting antibodies from exposure to influenza viruses before 1957.

Answer 27

Arose via recombination between viruses of Eurasian and North American swine HA protein strongly resembles HA protein of 1918 pandemic virus Little variation over 90 years because viruses circulated in swine

Answer 28

First drugs: M2 inhibitors (prevent uncoating step) * Amantidine (sold as Symmetrel) * Rimantidine (sold as Flumadine) New class of antivirals: N inhibitors (prevents neuraminidase from cleaving sialic acid during budding) * Causes viruses to clump at the cell surface, reducing viral spread * Oseltamivir (sold as Tamiflu, pill form) * Zanamivir (sold as Relenza, must be inhaled) * Peramivir received Emergency Use Authorization to treated hospitalized patients with a severe case of H1N1 in 2009. Treatment must begin within 36 hours of onset of symptoms. Used prophylactically in chronic care facilities

Answer 29

* Most effective way to prevent influenza * Flu vaccination time in the United States * October and November * Vaccine grown in eggs * Inactivated trivalent vaccine * Live attenuated vaccine (LAIV) * Licensed in 2003 * Only approved for healthy people ages 5–49 years

Answer 30

* Recommendations made based on antigenic analyses of recently isolated influenza viruses, epidemiologic data, and post-vaccination serologic studies in humans * Vaccine is a cocktail of 3 virus strains * 2 strains of influenza A * 1 influenza B strain * Efficacy depends on age * Children: 30-70% * Adults: 70-90% (when matched) * Elderly (\> 65 yrs):

Answer 31

Cold-adapted attenuated viruses; replication restricted to upper respiratory tract * Viral reassortants of circulating strains (H1N2, H3N2, B) Individuals 2-49 years of age * Not for children \< 24 months old or asthmatics * Concerns with immunocompromised individuals Induction of mucosal antibodies and T cell immunity

Answer 32

TIV vs. LAIV Age of the vaccine recipient Immunocompetence of the recipient Degree of similarity between the viruses in the vaccine and those in circulation

Answer 33

* Persons aged 50 or older * Individuals in chronic care facilities * including nursing homes * Individuals with pre-existing chronic problems * asthma, other pulmonary or cardiovascular problems, immunosuppression * Children on long-term aspirin therapy * Pregnant women * Healthcare workers * Travelers

Answer 34

* In 1946, WHO established influenza surveillance program. * U.S. sentinel physicians send flu statistics to the CDC. Patient visits for influenza-like illness Age groups Morbidity and mortality statistics Identify circulating strains for inclusion in annual flu vaccine formulations

Answer 35

* Virologists say it is inevitable. * Many pandemic planning teams are at the international, national, state, and local levels. * Mass media played a vital role communicating to public and healthcare professionals during the 2009 H1N1 pandemic.

Answer 36

* Avian influenza strains cannot be grown in embryonated eggs. * Avian strains kill the eggs. * Reverse genetics allows experts to grow avian strains in cell cultures. * Developed by Dr. Webster so that rapid avian flu vaccines can be made.

Answer 37

Researchers working on a universal vaccine based on the used of the influenza A, M2 protein.

Influenza Viruses Flashcards

(61 cards)