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MICR2222 - Medical Virology > L3/4 - Influenza > Flashcards

L3/4 - Influenza Flashcards

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USMLE® Step 1 flashcards
1
Q

Where does the variation mostly on influenza?

A

HA segment

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2
Q

What are the 5 criteria for naming influenza?

A
  1. Subtype (A/B/C)
  2. Location
  3. Number
  4. Year of isolation
  5. Information HA/NA
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3
Q

How many HA and NA groups are there?

A

18 HAs

9 NAs

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4
Q

How much % difference can HAs (and NAs) have?

A

30%

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5
Q

What animal species can all types of influenza infect?

A

Birds

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6
Q

How does HA0 make HA1 and HA2?

A

HA0 is cleaved by cellular proteases

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7
Q

What is the determinant of host range?

A

Specificity of receptor binding: HA-SA

a2-3 or a2-6 linkages

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8
Q

Which sialic acid linkages do BIRDS and HUMANS have?

A

Birds: a2-3
Humans: a2-6

PROTECTS HUMANS FROM MANY AVIAN INFLUENZAS

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9
Q

Why is host specificity not so straight forward?

A

HA proteins can attach to both a2-3 and a2-6

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10
Q

What strains tend to be low pathogenicity ‘seasonal’ flu?

A

H1, H2, H3

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11
Q

What strains have decimated chicken populations?

A

H5, H7

240mil chickens culled/died

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12
Q

How do HAs show differenced in their preferred hosts?

A

ability to cleave the host’s sialic acid

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13
Q

How many virus particles can one sneeze contain?

A

1,000,000

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14
Q

What are the 2 ways flu is transmitted?

A

Virus inhalation via respiratory tract

direct contact - fomites

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15
Q

How is direct contact for flu prevented?

A

Personal hygiene

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16
Q

What are symptoms of influenza mostly due to?

A

immune response

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17
Q

What is responsible for the different peak months in north/south hemispheres?

A

Climatic influence of summer and winter

UV exposure

LOW TEMPERATURE
LOW HUMIDITY

Social behaviour - indoor crowding, xmas

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18
Q

What conditions are best for flu transmission?

A

low temp - 5c
Low humidity - 20-35%

viruses are more stable and increased chance of droplet inhalation

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19
Q

What type of flu was the 1918 Spanish flu?

A

H1N1

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20
Q

what are the reasons for the severity of the 1918 Spanish flu?

A

cleavability of the HA protein

The HA protein could be cleaved by OTHER PROTEASES - infect other cells and ORGANS

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21
Q

What is antigenic DRIFT?

A

RdRP makes errors when copying

1/10000

incorporation of SINGLE NUCLEOTIDE CHANGES

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22
Q

Why are most anitgenic drift changes on HA1?

A

HA1 has low functional restrictions

most mutations are OUTSIDE THE RECEPTOR BINDING SITE

changes would affect ability of HA to bind to SA in binding site

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23
Q

What is antigenic SHIFT?

A

2 different flu viruses infect the same cell

RARE EVENT! (PANDEMICS)

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24
Q

How does the pig allow human and avian strains to mix?

A

both a2-3 and a2-6 linkages

25
Q

What 4 viruses make up swine flu?

A

US pig
Eurasian pig
US avian
Human

3 combined
4th virus eurasian swine then combined

26
Q

What is the barrier between the highly pathogenic H5N1 infecting the human population?

A

SPECIES BARRIER

27
Q

What are the 3 requirements for human-human spread of H5 strains?

A

1) enter cells of human URT
2) replicate in HIGH NUMBERS in URT cells
3) exit URT cells

28
Q

Can sialic acid binding easily change through mutation?

A

yes

29
Q

How many aa changes are required to switch HA specificity?

A

1 or 2 aa changes

30
Q

Why is the replication rate of avian H5N1 reduced in humans?

A

different temperature

37 vs. 41

31
Q

What mutation in PB2 can affect peak replication temeprature?

A

E627K

32
Q

What were the 3 mutations of H5N1 given to ferrets origianlly?

A

Q222L
G224S
E627K

33
Q

Why were the 3 original mutations of the H5N1 virus not enough?

A

NO aerosol transmission

34
Q

Brief overview of ferret experiment to select an aerosol transmissible virus?

A

infected with H5N1 (222/224/627)

4 days - sneeze sample

infect

wait 4 days - repeat

x10

(ANTIGENIC DRIFT)

35
Q

What are the 2 additional mutation to the H5N1 (222/224/627)

A

H103Y

T156A

36
Q

How is the influenza vaccine produced?

A

GISRS predicts 3/4 dominating strains yearly

37
Q

What is the traditional method of influenza vaccine production?

A

3 chosen strains - weakened

segment exchange (REASSORTMENT) with PR8

256 genotypes

INFECT EGGS

38
Q

Which segments are PR8 and which are the circulating strain?

A

circulating strain - HA, NA

rest - PR8

39
Q

What are the 3 drawback of tradition flu vaccine making?

A

SLOW reassortment - 3 months

dependent on eggs (170mil)

some H5N1 grow poor in eggs

40
Q

What is the ‘new’ way to make flu vaccines?

A

cDNAs - encode the 8 RNA genome sequences wanted

make 8 functional RNPs

41
Q

How is the cDNA-based system for vaccines better?

A

seed in 2 weeks

no eggs

no issues with egg allergy/growing poorly

42
Q

What are the 3 current targets for anti-influenza therapeutics?

A

3) Endosome escape
5) RNA synthesis
8) Release

43
Q

(FLU) What anti-virals are used for (step 3) endosome escape?

A

The Adamantanes

AMANTADINE
RIMANTADINE

44
Q

What are the pros/cons of the Adamantanes?

A

PRO - cheap, effective

CONS - administered before day 2

45
Q

How is Rimantadine different to amantadine?

A

added methyl group

46
Q

What influenza does the Adamantanes work against?

A

ONLY FluA

47
Q

How do Adamantanes work?

A

prevent M2 ion channel activity

blocks/closes pore

cannot exit endosome

48
Q

What are issues with Adamantanes?

A

most human flus now resistant

mutations within M2 channel

NO LONGER FDA APPROVED

49
Q

(FLU) What anti-virals inhibit the endonuclease active site (step 5 - RNA synthesis)

A

XOFLUZA

50
Q

How does Xofluza act?

A

binds the PA endonuclease active site

51
Q

What flus is Xofluza effective against?

A

fluA, fluB

52
Q

What does step 8 virus release involve?

A

NA

ability of NA to bind to SA and cleave it

53
Q

(FLU) What anti-virals are effective against (step 8) virus release?

A

Relenza - ZANAMIVIR (aerosol)

Tamiflu - OSELTAMIVIR (oral)

Repivab - PERAMIVIR (IV)

WORK BY MIMICING SIALIC ACID

BLOCK NA ACTIVE SITE

54
Q

What is the stockpile of tamiflu and relenza worth?

A

£500m

55
Q

What is the issue with flu resistance in NA inhibitors?

A

NA muatates so it no longer binds to tamiflu/influenza

56
Q

What are future flu anti-virals not yet FDA approved?

A

polymerase inhibitor - FAVIPIRAVIR

DAS-181 - HA attachment inhibitor

57
Q

How do NA inhibitors act?

A

bind with higher affinity to NA than sialic acid

exploite weak site 2 in the 5 site NA binding pocket

58
Q

Why do NA inhibitors bind better than SA?

A

charged guanidino group added - interacts with neg charged Asp and Glu more strongly

100x higher affinity

MICR2222 - Medical Virology (13 decks)

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