Influenza Flashcards
influenza virus type
orthomyxoviruses
enveloped
negative strand RNA genome
Influenza A
most common and rapidly evolving
pandemics
infects humans, pigs, birds
zoonosis
changes every year
Influenza B
humans only
generally more mild
less variablity
less severe
Influenza C
humans and pigs
less clinical
children
hemagglutinin
surface glycoprotein
bind to host cell and enter it
hold onto host cell
neuraminidase
surface glycoprotein
cleave sialic acid to get the virus out of the cell
M1
layer that lines the envelope
contacts NA/HA and RNA/NPs
M2
matrix 2 ion channel in envelope
pump - pumps H+ into virion during uncoating
polymerase complex
PA, PB1, PB2 RNA strands
polymerase complex heterotrimer
NP
nucleoprotein
coat neg strand RNA to protect it
NS2
regulatory factor
sits in the space, contained in the virion
RNPs
ribonucleoproteins
8 negative strand RNA segments with NPs and 3 polymerase segments
NS1
remains in the infected cell and blocks host IFN response
influneza transmission
aerosol droplets from nose and throat of an infected person
mostly upper respiratory
Basic influenza replication cycle
- bind to sialic-acid containing receptors,
- virus is endocytosed and envelope fuses with memrane
- Pump H+ in to acidify. modifies the particle. Acidification allows RNA/proteins particles (RNPs) to be released into cytoplasm and translocate into nucleus
- Transcription of RNA segments generates mRNAs that are translated by ribosomes in the cytoplasm
- New genome segments (cRNAs) are made in the nucleus and are exported into cytoplasm (mRNA –> cRNA, replication, formation of RNP!)
- Assembly with viral proteins at plasma membrane
- NA (here labeled sialidase) cleaves sialic acid allowing viral particles to be released
Pulmonary complications
viruses target and kill mucus-secreting ciliated epithelia
They also use the neuraminidase to degrade and penetrate the mucus layer, rendering the upper respiratory tract vulnerable to a variety of pathogens
There is also a localized inflammation response
Resultant cell damage promotes adherence of bacteria to epithelia, compromising the ‘sterile’ environment of the lungs.
Croup, viral (primary) pneumonia, secondary (bacterial) pneumonia, cardiac failure, water diarrhea, conjunctivitis
how influneza infections self resolve?
- innate defenses (interferon, cytokines) most important!
- cell mediated (T cell)
- Neutralizing abs - protection!
antigenic drift
replication errors causing individual nucleotide changes
replicates so much
RNA pol is not precise
increased error rates, evolve fast
lots of nmutants and immune leads to very strong selection
IAV and IAB
antigenic drift
reassortment of genome fragments (whole genes)
genes are in individual segments - 2 serotypes infect cells and mix and match, random assortment w type of each fragment
IAV only
1918 pandemic
killed healthy young adults! massive increase in young dying
“U” shaped mortality normally
1918 - “W”
Aggressive T cell response damaged cells, allowed other pathogens in
Avian influenza
avian viruses favor sialic acid with a2-3 linkage and human viruses prefer a2-6 linkage
in humans - the few a2-3 usually found deep in the lung - more susceptible to pneumonia etc
high mortality but more spread
Uncoating inhibitors
antiviral
amantadine and rimandtidine
block M2 hannel and acidification of virus inside vesicles
plug channel to block replication
easily mutate away - not used anymore
not effective against IBV - no M2
NA inhibitors
Tamiflu, Relenza, Peramivir
effective against IBV, IAV
inhibit budding, prevents removal of sialiic acid from receptors - doesn’t stop from infection but limits it
gives immune system time to deal with the virus
effective prophylaxis
must be taken 48h or less into infection
Flu vaccine
killed virus
injection
quadrivalen - A + A + B + B
most common surface subtypes
LAIV
live attenuated, nasal mist
nasal sray
genetically modified, replicate a litle but only at low temps like tip of the nose
approved for ages 5-49 - those with a robust immune defense
bnAbs
approach for universal vaccine
broadly neutralizing abs - against stem region of HA?
RSV
Paramoxovirus
negative strand RNA
leading cause of LRT in infants and young children, bronchiolitis, otitis media
spreads down RT by cell to cell transfer along intracytoplasmic bridges (syncytia) from URT to LRT
usually only URT in older children and adults
Ankara strain
of vaccinia virus (Pox virus)
expresses flu M and NP priteins
elicits T cell (not ab) response
controls rather than eliminates the virus
SARS
new virus
pos strand RNA envelped virus
