Section 6.3

Question 1

Diversity of Animal Virus Genomes:

Answer 1

ssDNA: parvo and circo

dsDNA: herpes, papiloma, polyoma, adeno, pox

dsDNA (RT)
+ RNA (RT): retro

+ssRNA: Corona, flavi
dsRNA:
-ssRNA: Influenza (orthomyxo), Filo

Question 2

Influenza viruses genome (and structure):

Answer 2

Orthomyxoviridae
Segmented -ve sense ssRNA
——–Enveloped—–
with glycoproteins on the surface (HA and NA)

Question 3

Types of Influenza viruses (A, B and C +2)

Answer 3

Influenza A: birds and mammals
Influenza B: humans
Influenza C: humans (and pigs?)
thogotovirus: verist
isavirus: fish

Question 4

HA: hemagglutinin is important for

Answer 4

important for binding to cell surface receptors and entry

Question 5

NA: neuraminidase is important for

Answer 5

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

Question 6

Important drug used for serious influenza infections that INHIBITS neuraminidase

Answer 6

Tamiflu

Question 7

What are the receptors on the cell that bind to HA and aid in virus entry

Answer 7

sialic acids attached to proteins in membrane
- leads WHOLE VIRION to get endocytosed

Question 8

How does IA viral entry occur

Answer 8

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

Question 9

ebola v.s HIV v.s Influenza membrane fusion

Answer 9

HIV fusion occurs at CM due to conformational changes after viral envelope proteins interact w cellular receptors

Question 10

Influenza genome has 8 segments that encode ___-____ proteins

Answer 10

11-16 proteins

Question 11

Influenza genome segment organization and steps

Answer 11

• 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

Question 12

what species is the natural reservoir and hosts for influenza viruses

Answer 12

birds

Question 13

influenza viruses that circulate naturally in wild birds and cause no signs of disease are called ____ ______ ______ (____)

Answer 13

Low pathogenicity strains (LPAI)

– but can evolve to high pathogenic strains (HPAI) and cause systemic infection (not just GI)

Question 14

influenza virus infects and replicates in cells of the ________ _____ and are released through feces and spread by fecal- ____ contamination

Answer 14

gastrointestinal tract
Fecal - ORAL transmission

Question 15

two versions of sialic acid cell surface receptors for HA protein

Answer 15

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!)

Question 16

what makes an influenza strain adapted to a certain host?

Answer 16

• 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)

Question 17

what types of SA do humans have?

Answer 17

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)

Question 18

What is the second factor that affects influenza host range?

Answer 18

Body temperature

birds 40
human URT 33
pigs (in the middle)

Question 19

Other (third) factor in cells that limit influenza replication ability

Answer 19

• 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)

Question 20

what mutation suddenly makes influenza viruses super pathogenic

Answer 20

mutation allowing HA to be cleaved by any ubiquitous proteases in cells (leading to systemic infection everywhere)

Question 21

What influenza strains infect humans?

Answer 21

H1M1 and H3N2 (H2N2 was also but it has been extirpated)

Question 22

Influenza evolution
1) Antigenic drift:

Answer 22

RdRp is error prone - makes at least 1 mistake every genome replication

Question 23

Influenza evolution
2) Antigenic shift:

Answer 23

due to segmented genome, co-infection leads to packaging of diff combinations of gene segments leading to novel assortments

Question 24

antigenic drift and antigenic shift effect all 8 genes but are most important for:

Answer 24

HA and NA - as they are the major immune targets

therefore we need new vaccines every year

Question 25

we need to get vaccinated every year because the virus evolves and because:

Answer 25

we need high levels of circulating antibodies (despite memory B cells)

Question 26

Who tracks influenza viruses to make new vaccines every year with new strains?

Answer 26

Global Influenza Surveillance and Response System (GISRS) coordinated by the World Health Organization (WHO)

Question 27

What is the biggest difficulty to making influenza vaccines? and we figured out the reason so why?

Answer 27

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

Question 28

how can we make the holy grail vaccine

Answer 28

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)

Question 29

what makes influenza seasonal?

Answer 29

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

Question 30

1918 spanish flu H1N1

Answer 30

likely due to circumstances with WWI and ppl who died are ppl in their 20s ODD!

Question 31

why is the 1918 Spanish flu so deadly for young ppl?

Answer 31

triggers extreme immune response (young ppl have the immune system)

Question 32

what does the quote “first flu is forever” mean?

Answer 32

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

Question 33

2009 H1N1 pandemic was a ____ _____ between birds to pigs to humans back to pigs therefore a _____ _______

Answer 33

Triple reassortment
reverse zoonosis

Question 34

A deadly bird virus that directly infected people

Answer 34

H5N1

Question 35

H5N1
a) 3 properties of a human pandemic virus

Answer 35

1- new antigenicity (no immunity in population)
2- high infectivity in URT
3- transmission between humans

Question 36

others facts about H5N1

Answer 36

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

Question 37

Highly pathogenic H5N1 hit North America in later 2014 majorly effecting

Answer 37

poultry farms (difficult and expensive)

in 2021 it crossed the Atlantic

Question 38

Other surprise bird flu in 2013:

Answer 38

H7N9

Question 39

unlike H5N1, H7N9 birds did not show symptoms but had larger human mortalities

Answer 39

old people imprinted with H1 so very susptible to H7

young ppl imprinted w H3 so more suspetible to H5