Orthomyxoviruses Flashcards
true or false: influenza viruses have almost an unlimited amount of serotypes
true
true or false: influenza is an endemic disease
false it is an epidemic disease
worst months: February
True or false: influenza is a pandemic disease
true
when did asian flu was a thing
in 1957 in usa, rhode island
girl scouts fucked up
What does Flu do
-it affects and kills cells of our respiratory tract
-wipes out mucocilary defenses
What is a part of the structure of influenza?
-HA: hemagglutinin 16 completely distinct gene types A
-NA: neuraminidase 9 completely distinct gene types A
-NS1: major non structural protein
-Helical nucleocapsid
-lipid bi layer membrane
-polymerase: 3 peoteins
-M1 protein: matrix protein
true or false: NS1 is expressed in influenza infected cells
true
What are the three groups of influenza
A, B and C which is based on the nucleoprotein type
True or false: influenza viruses from different groups can recombine
false: they can’t
which type of influenza viruse4s can infect only humans
B and C
Which type of influenza virus can infect all mammalian and avian species
A
True or false: only C influenza viruses can cause pandemics
false it is A
True or false: there is no antigenic cross-reactivity between different hemagglutinin and neuraminidase types
true
first influenza pandemic
h3n2
spanish flu name of strain and when did it started
1918 H1N1
First isolation of influenza
in 1933 H1N1
Asian flu 2
H2N2 1957
Hong kong flu
h3n2 1967 and in 1976 there was h1n1 too
MEXICAN FLU
h1n1 2009
how do they make influenza vaccines
you take the attenuated donor virus with the new antigenic variant and then you get the attenuated vaccine virus
What is the reservoir for Influenza A viruses
waterfowl basically they have a cloaca where the bladder, the vagina and the colon kinda all merge together
Avian influenza true or false: multiplies in cloacae without causing disease
trie
True or false: in avian influenza only one strain can exist in individual bird
false, multiple can coexist
true or false: there is high level of genetic reassortment in avian influenza
true
True or false: there is little to no selective pressure and little;e genetic change in avian flu
true
the 2009 h1n1 was a mix of what?
eurasian flu, h1n1, human h3n2 and avian
how did the 1956, 1967 and 2009 pandemic strains arose
-by recombination between human and avian strains possibly within a pig intermediate host
- these 3 pandemic strains: human strains with new avian HA+/- NA genes
true or false: the 1956 flu pandemic caused the most deaths
false
*The 1918 pandemic strain caused far
and away the worst human mortality
of a known flu pandemic
- 10-20 times that of 1956 or 1967
why was the 1918 strain unusual
- It commonly killed young and healthy
victims - Healthy asymptomatic persons:
- Could be struck suddenly
- Rendered too feeble to walk within hours
- Many would die the next day
- Symptoms included:
- Cyanosis
- Hemoptysis
- Later uncontrolled pulmonary
hemorrhage and edema - ARDS
mortality 1918 flu
Mortality in fast-progressing cases
-Primarily from ARDS-like disease
-Mortality in slower-progressing cases
-Primarily from 2o bacterial pneumonia
-Possible neural involvement:
- Frequency of psychiatric disorders
- Encephalitis lethargica
how many people dies from the 1918 flu
100 million worldwide
approx 60% of peeps got it and the mortality rate was 2.5-6%
WHAT DID THE COMPLETE 1918 INFLUENZA VIRUS CODING SEQUENCE REVEALED?
1) 1918 strain NOT a human/avian recombinant
but a PURE avian strain
(2) 23 a.a. changes out of 5,672
(3) Sequence did not explain virulence
(4) Decision to use reverse genetics to generate a live
flu virus with the genome of the 1918 pandemic virus
TRUE OR FALSE: THE 1918 strain would not fuck us up rn
FALSE IT WOULD
h5n1 1996
in china in chickens a lot of people got sick
they killed all them chickens
true or false: no evidence of sustained human to human transmission in h7n9
true
What would be required to
produce a new pandemic
strain of influenza that would
be as pathogenic as the 1918
strain?
1) HA protein to which humans have little or no immunity
(2) HA mutation 1 facile infection of non-respiratory tissues
(including macrophages) allowing spread outside lung
(3) HA mutation 2 higher affinity oligosaccharide-binding
to the human sialyl-6-lactose receptor than
to the avian sialyl-3-lactose receptor
(4) Polymerase proteins direct facile RNA synthesis in human cells
(5) Viral NS1 protein has mutations directing
- high level induction of apoptosis
- high level inhibition of IFN induction
(6) Induction of severe pro-inflammatory effects (cytokine storm)
(7) Ability to easily infect humans
(8) Ability to cause significant disease in humans
(9) Ability to spread easily from humans to humans
Difference between h1n1 1918 and current h7N9
does not spread easily human to human
what are the drugs attck against flu
neuranimidase inhibitor
blocks the cleavage of the receptor aka hemagglutinin and the cell receptor so that no new virion can be released
-tamiflu
what are the 2 surface proteins of the flu
Na and HA
how many mechanisms are there to make express proteins
6
true or false: influenza replicates in the nucleus
true
Unlike almost all other RNA viruses, influenza virus
nucleocapsids are transported to and are transcribed and
replicated in the host cell nucleus
how does influenza gets in cell
sialic acid receptor and clathrin coated pir
which proteins binds to the cell receptor
HA
is influenza an rna virus or DNA
- ssRNA
true or false: there is a pH conformation change in influenza
true in endosomal membrane
Influenza virus RNA transcription:
- PB2 recognizes and binds 5’ cap structures found on all
eukaryotic mRNAs - PB2 binds to caps of newly-synthesized pre-mRNAs in the cell
nucleus - PB1 then acts as a nuclease, cleaving the bound pre-mRNA at
an A or G residue 10–13 nt from its 5’ cap - This capped RNA fragment, still bound to PB2, is used as
primer to copy genome RNA
-
role of PB1
-PB1 acts as an RNA polymerase
Role of PA
- Role of PA is not well understood
- Resulting viral mRNAs have heterogeneous sequences for the
first 10–13 nt - Flu can thus make capped messenger RNAs even though they
do not code for a capping enzyme
What does NS1 do
The NS1 protein interferes with polyadenylation of cellular
mRNAs
NS1 protein is the most abundant viral protein in virus-infected
cells
NS1 binds to both single- and double-stranded RNA and to two
host cell proteins:
(1) cleavage and polyadenylation specificity factor (CPSF)
(2) poly(A)-binding protein II (PABII)
Binding of NS1 to these proteins inhibits normal 3’ end cleavage
and polyadenylation of cellular mRNAs
Polyadenylation of viral mRNAs occurs by a distinct mechanism
and does not depend on these cellular enzymes
Cap-binding and endonuclease activities of the influenza PB2 and PB1 proteins leads to
Cap-binding and endonuclease activities of the influenza PB2 and PB1 proteins leads to degradation of cellular pre-mRNAs in virus-
infected cells
As a combined result of interference with 3’ end processing and 5’ end cleavage
- most cellular pre-mRNAs are degraded in the nucleus
- cellular mRNA production and protein synthesis are suppressed
Influenza virus and the immune system:
NS1 inhibits activation of the interferon-induced PKR antiviral pathway
During influenza virus transcription, some ds-RNAs are inevitably formed
Virus infection → interferon production
→ cells produce double-stranded RNA-dependent protein kinase (PKR)
In the presence of ds-RNA, PKR is activated and blocks both cellular and viral protein synthesis
