Influenza

Question 1

influenza virus type

Answer 1

orthomyxoviruses

enveloped

negative strand RNA genome

Question 2

Influenza A

Answer 2

most common and rapidly evolving

pandemics

infects humans, pigs, birds

zoonosis

changes every year

Question 3

Influenza B

Answer 3

humans only

generally more mild

less variablity

less severe

Question 4

Influenza C

Answer 4

humans and pigs

less clinical

children

Question 5

hemagglutinin

Answer 5

surface glycoprotein

bind to host cell and enter it

hold onto host cell

Question 6

neuraminidase

Answer 6

surface glycoprotein

cleave sialic acid to get the virus out of the cell

Question 7

M1

Answer 7

layer that lines the envelope

contacts NA/HA and RNA/NPs

Question 8

M2

Answer 8

matrix 2 ion channel in envelope

pump - pumps H+ into virion during uncoating

Question 9

polymerase complex

Answer 9

PA, PB1, PB2 RNA strands

polymerase complex heterotrimer

Question 10

NP

Answer 10

nucleoprotein

coat neg strand RNA to protect it

Question 11

NS2

Answer 11

regulatory factor

sits in the space, contained in the virion

Question 12

RNPs

Answer 12

ribonucleoproteins

8 negative strand RNA segments with NPs and 3 polymerase segments

Question 13

NS1

Answer 13

remains in the infected cell and blocks host IFN response

Question 14

influneza transmission

Answer 14

aerosol droplets from nose and throat of an infected person

mostly upper respiratory

Question 15

Basic influenza replication cycle

Answer 15

1. bind to sialic-acid containing receptors,
2. virus is endocytosed and envelope fuses with memrane
3. Pump H+ in to acidify. modifies the particle. Acidification allows RNA/proteins particles (RNPs) to be released into cytoplasm and translocate into nucleus
4. Transcription of RNA segments generates mRNAs that are translated by ribosomes in the cytoplasm
5. New genome segments (cRNAs) are made in the nucleus and are exported into cytoplasm (mRNA –> cRNA, replication, formation of RNP!)
6. Assembly with viral proteins at plasma membrane
7. NA (here labeled sialidase) cleaves sialic acid allowing viral particles to be released

Question 16

Pulmonary complications

Answer 16

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

Question 17

how influneza infections self resolve?

Answer 17

1. innate defenses (interferon, cytokines) most important!
2. cell mediated (T cell)
3. Neutralizing abs - protection!

Question 18

antigenic drift

Answer 18

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

Question 19

antigenic drift

Answer 19

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

Question 20

1918 pandemic

Answer 20

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

Question 21

Avian influenza

Answer 21

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

Question 22

Uncoating inhibitors

Answer 22

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

Question 23

NA inhibitors

Answer 23

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

Question 24

Flu vaccine

Answer 24

killed virus

injection

quadrivalen - A + A + B + B

most common surface subtypes

Question 25

LAIV

Answer 25

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

Question 26

bnAbs

Answer 26

approach for universal vaccine

broadly neutralizing abs - against stem region of HA?

Question 27

RSV

Answer 27

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

Question 28

Ankara strain

Answer 28

of vaccinia virus (Pox virus)

expresses flu M and NP priteins

elicits T cell (not ab) response

controls rather than eliminates the virus

Question 29

SARS

Answer 29

new virus

pos strand RNA envelped virus