Exam IV: Lecture 13 Flashcards
Tell me about the 1918-1919 Spanish Flu
H1N1
20-40 million deaths
What were some other deadly flus beside the Spanish flu?
Asian Flu
Hong Kong Flu
Influenza virus is a member of what family? What is its genome like?
Orthomyxovirus family
Segmented -RNA
Is the influenza virus enveloped?
Yes
What are the two important proteins in the envelope of the influenza virus?
Nuerominidase (9)
Hemagglutinin (15)
What are the 3 major genera of influenza virus?
A, B, C
The genome of A and B generas of influenza virus are made up of how many gene segments? How many kb? How many proteins does it code for?
8 segments
14 kb
10 protiens
What host receptor does the influenza virus use to enter the cell?
Sialic acid
How many segments does the C genome of influenza code for? How many proteins?
7 segments
9 proteins
How does influenza virus spread?
Through cold, dry air
How large is the influenza viurs?
100nm in diameter
What cells does the flu virus infect? What does it cause?
Ciliated epithelium > kills ciliated epithelial> reduction of mucociliary flow > increased chance of secondary infection > this is what kills you (pneumonia)
Influenza di freddo
Effect of Cold
What does M1 do?
Matrix protein - interacts with envelope to give viral shape
What do PB1, PB2, and PA do?
Cap snatching proteins > cleave cap of pre-mRNA to form primer
What are HA and NA used for?
Surface glycoproteins. HA for entry. NA for exit.
What do NS1 and ND2 do?
Block cellular mRNA transport, interfere with interferon pathway, inhibits PKR, promotes viral RNA transport to the cytosol
Tell me about HA1 and HA2 and their relationship to each other and their roles in entry and fusion
HA1 is a binding protien
HA2 is hidden by HA1 until there is a conformational change triggered bu the acidification of the endosome > cleavage of disulfide bridge between HA1 and HA2 > HA2 acts as a fusion peptide = brings viral and endosomal membrane together > genome released into the nucleus
What are vRNPs?
Viral RiboNuclear Protien
How does amantadine function in influenza?
Disables viral uncoating
Blocks M2 protien
How do NAIs function in influenza?
Inhibit the release of virions and promote virion clumping
What is vcRNA?
viral complementray RNA
Talk me through replication of influenza virus
PB1 binds to genomic RNA > creates antigenomic copy which is gated by NP to keep neg and pos strands from binding together > PB1 cleaves caps off of host mRNA > PB1+PB2cap all goes to bind to viral RNA > PB1 transcript until string of UUUUU > results in a polyA tail = produces mature mRNA > viral mRNA can be translated normally
What is the process of viral genomic RNA synthesis?
Virus particles assemble in the nucleus and the nucleocapsid buds through the plasma membrane. If the cells are infected with more than one flu virus at a time this is the perfect time for reassortment
Flu season in northern latitudes is from November to March, the coldest months. IN southern latitudes, it is from May until September.
Yep
How long is the incubation of influenza?
1-3 days (short)
What are the symptoms of the influenza virus?
Fever, myalgia, headache, pharyngitis, prostration, cough
NOT a runny nose
What other differences are there in symptoms between cold and influenza?
Cold = runny nose Flu = severe myalgia Flu = last weeks
What is the timeline of the pathogenesis of influenza?
IFN 2-8 days
T-cells 6-28 days
Pathologic change in resp tract 8-28 days
What is the timeline of laboratory detection of influenza?
Virus in respiratory secretions 1-9 days
Rise in virus-specific antibody 8–> days
What is the timeline of the clinical disease of influenza?
Incubation 0-5days
Symptomatic disease 2-24 days
Secondary bacterial infection 6-13 days
Influenza Infection can range from asymptomatic to moderte to severe
True
Is the onset of symptoms sudden or gradual?
Very sudden
How long does a fever last with influenza?
3-5 days
influenza virus can cause pneumonia itself, or make the patient susceptible to bacterial pneumonia
True
Is influenza capable of zoonosis? Why?
Yes, because the receptor is SA which is common in many species
Can you acquire viruses from your pets?
Yes, cats, dogs, cattle, pig, rodents, primates
RNA viruses are prone to errors during replication. Why?
There are no proofreading mechanisms
How does the virus over come the high amount of errors in replication?
Replication occurs at a very high rate so even if only 1% of mutations are beneficial that is still going to produce a lot of virions
Ex) singular nucleotide change and change the glycoprotein and allow the virus particle to evade host antibodies
What is antigenic shift?
A major change in the genome a virus caused by the exchange of segments between two strains of influenza viruses that are infecting the host cell at the same time
How do you get a new strain of the influenza virus?
Antigenic shift
How does zoonosis effet the diversity of influenza strains?
Because SA is a common receptor > zoonosis > avian influenza mix with Spanish influenza in a bird > entirely new strain of influenza
After reassortment, not all subtypes of HA and NA can infect humans, which subtypes can?
HA 1,2,3
NA 1,2
How do we guess which strains to put in the flu shot each year?
Look at where antigenic shift could have occurred (we won’t have immunity against a new strain) > farms have pigs, ducks, and humans > take samples from each species > predict with strain will become a pandemic (how many times do we see this stain in different populations?)
What does Tamiflu inhibit?
NA inhibitors
Block entry
How did we resurrect the 1918 strain of influenza (Spanish flu)?
Took a sample from lung tissue from body in permafrost and extracted the RNA sements
Mixed the RNA segments with flu RNA in the lab and creased a hyprid virus
What did we learn about the spanish flu after resurrecting it? i.e. what made it so ready?
It was able to cleave HA with NA by itself > had the ability to autoactivate fusion > did not need trypsin (host protease) to do it (in lung cells) > which meant it could infect any cell in the body
What is a cytokine storm? How is it implicated in Influenza A deaths?
The overproduction of cytokines causes increased inflammation which acts a positive feedback loop to recruit event more immune cells which will then be triggered to release cytokines
Cytokine storm can develop into acute respiratory distress system (ARDS) since influenza infection occurs in the lungs > death