Section 6.3 Flashcards
(39 cards)
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
