Section 6.3 Flashcards
Diversity of Animal Virus Genomes:
ssDNA: parvo and circo
dsDNA: herpes, papiloma, polyoma, adeno, pox
dsDNA (RT)
+ RNA (RT): retro
+ssRNA: Corona, flavi
dsRNA:
-ssRNA: Influenza (orthomyxo), Filo
Influenza viruses genome (and structure):
Orthomyxoviridae
Segmented -ve sense ssRNA
——–Enveloped—–
with glycoproteins on the surface (HA and NA)
Types of Influenza viruses (A, B and C +2)
Influenza A: birds and mammals
Influenza B: humans
Influenza C: humans (and pigs?)
thogotovirus: verist
isavirus: fish
HA: hemagglutinin is important for
important for binding to cell surface receptors and entry
NA: neuraminidase is important for
important for penetration through mucous layer (so that they can get to cell surface receptors) and release from cell mucous after replication
- Chews through the mucous
- Degrades the sugars/mucous on the surface as the virus buds out to free it from getting stuck in sugar
Important drug used for serious influenza infections that INHIBITS neuraminidase
Tamiflu
What are the receptors on the cell that bind to HA and aid in virus entry
sialic acids attached to proteins in membrane
- leads WHOLE VIRION to get endocytosed
How does IA viral entry occur
1- HA binds to sialic acids on cell surface receptors and whole virion goes in through a vesicle
2- low pH inside endocytic vesicles causes conformational change in HA exposing its peptide fusion region
3- membrane of virion fuses with that of the vesicle and RNAs get released into cytoplasm
ebola v.s HIV v.s Influenza membrane fusion
HIV fusion occurs at CM due to conformational changes after viral envelope proteins interact w cellular receptors
Influenza genome has 8 segments that encode ___-____ proteins
11-16 proteins
Influenza genome segment organization and steps
- influenza RNA segments are tightly packed through nuclei protiens vRNP and not loose inside the capsid
- each segment is with its own replicase attached to it to make +ve sense copies that
—— go into cytoplasm for protien synthesis
——– stay In nucleus to make more -ve sense RNA
what species is the natural reservoir and hosts for influenza viruses
birds
influenza viruses that circulate naturally in wild birds and cause no signs of disease are called ____ ______ ______ (____)
Low pathogenicity strains (LPAI)
– but can evolve to high pathogenic strains (HPAI) and cause systemic infection (not just GI)
influenza virus infects and replicates in cells of the ________ _____ and are released through feces and spread by fecal- ____ contamination
gastrointestinal tract
Fecal - ORAL transmission
two versions of sialic acid cell surface receptors for HA protein
a2-3 and a2-6
at the ends of sugar-portions of glycoproteins in the membrane
(diff cells have diff types of SA, diff SA have diff shapes and structures to determine which cell is infected)
Vary per species (pigs have both!)
what makes an influenza strain adapted to a certain host?
- the specificity of binding to the predominant SA present in the host (making the cell susceptible)
**determines host range - the cells that allow virus to replicate
(making the cell permissive)
what types of SA do humans have?
Upper respiratory tract has a2-6
(most viruses that infect us)
Lower respiratory tract has a2-3
(so bird viruses can still get to us)
What is the second factor that affects influenza host range?
Body temperature
birds 40
human URT 33
pigs (in the middle)
Other (third) factor in cells that limit influenza replication ability
- HA protein needs to be cleaved from the translated full length protein (H0) to HA1 and HA2 to actually work
- only cleaved by cellular proteases present in limited cells
(intestine of birds and airway of human)
what mutation suddenly makes influenza viruses super pathogenic
mutation allowing HA to be cleaved by any ubiquitous proteases in cells (leading to systemic infection everywhere)
What influenza strains infect humans?
H1M1 and H3N2 (H2N2 was also but it has been extirpated)
Influenza evolution
1) Antigenic drift:
RdRp is error prone - makes at least 1 mistake every genome replication
Influenza evolution
2) Antigenic shift:
due to segmented genome, co-infection leads to packaging of diff combinations of gene segments leading to novel assortments
antigenic drift and antigenic shift effect all 8 genes but are most important for:
HA and NA - as they are the major immune targets
therefore we need new vaccines every year
we need to get vaccinated every year because the virus evolves and because:
we need high levels of circulating antibodies (despite memory B cells)
Who tracks influenza viruses to make new vaccines every year with new strains?
Global Influenza Surveillance and Response System (GISRS) coordinated by the World Health Organization (WHO)
What is the biggest difficulty to making influenza vaccines? and we figured out the reason so why?
H3
likely due to it being grown in chicken embryo eggs and developing a mutation at one epitope so it doesn’t work as good when it goes back to humans as immunization
how can we make the holy grail vaccine
target the more conserved stalk region rather than the head cuz it doesn’t evolve as fast
(hasn’t worked yet cuz its not very immunogenic - body doesn’t generate immune response to it cuz its hidden)
what makes influenza seasonal?
humidity and temp
—– in cold places, the viral envelope is prown to disruption by moisture
- therefore dry air and (low AH) lets virus replicate in cold placed
—— in warm environments viral envelope is prone to desiccation
- so more wet air (high AH) promotes viral spread when temp is high
1918 spanish flu H1N1
likely due to circumstances with WWI and ppl who died are ppl in their 20s ODD!
why is the 1918 Spanish flu so deadly for young ppl?
triggers extreme immune response (young ppl have the immune system)
what does the quote “first flu is forever” mean?
The first HA you are exposed to will be the one you have the best immunity to
Specially H3 and H1, because they are in opposite phylogenetic groups
2009 H1N1 pandemic was a ____ _____ between birds to pigs to humans back to pigs therefore a _____ _______
Triple reassortment
reverse zoonosis
A deadly bird virus that directly infected people
H5N1
H5N1
a) 3 properties of a human pandemic virus
1- new antigenicity (no immunity in population)
2- high infectivity in URT
3- transmission between humans
others facts about H5N1
b) limited as it is avian with a2,3 SA which is low in URT
c) close contact w a lot of H5N1 will lead to LRT but it doesn’t transmit between humans
d) a strain found of H5N1 that has increased interactions with human cells but still doesn’t transmit
Highly pathogenic H5N1 hit North America in later 2014 majorly effecting
poultry farms (difficult and expensive)
in 2021 it crossed the Atlantic
Other surprise bird flu in 2013:
H7N9
unlike H5N1, H7N9 birds did not show symptoms but had larger human mortalities
old people imprinted with H1 so very susptible to H7
young ppl imprinted w H3 so more suspetible to H5
