25. Flavivirus Flashcards

(76 cards)

1
Q

what is a well-known flavivirus?

A

yellow fever

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2
Q

describe the clinical features of yellow fever

A

PERIOD OF INFECTION:
- minor symptoms: headache, nausea, dizziness

Some can resolve infection but some progress to
PERIOD OF INTOXICATION:
- severe infection: jaundice, haemorrhage, malaise
- 50% recover, 50% die

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3
Q

what was the Yellow Fever Commission? what were the results?

A

to prove that yellow fever was transmitted by mosquitos

volunteers were bitten by mosquitos that had fed on yellow fever patients –> got mild disease but quickly recovered –> still insufficient evidence

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4
Q

what were the Mosquito Brigades?

A

fumigate mosquitos to eradicate disease in Panama –> it worked!

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5
Q

why did yellow fever remain in areas where they eliminated the mosquitos?

A

mosquitos were only a vector –> non-human primates are the stable and persistent reservoir

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6
Q

development of YFV vaccine (4 stages)

A
  1. isolated virus from yellow fever survivor
  2. grew virus in mice
  3. passaged in monkeys
  4. > 100 passages in chicken eggs to form 17D vaccine strain
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7
Q

describe the 17D vaccine strain of yellow fever

A

attenuated virus that can grow and replicate without pathogenesis –> but still had some neurotropism and viscerotropism

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8
Q

baltimore class of flavivirus?

A

class 4 (+RNA)

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9
Q

is flavivirus enveloped or naked?

A

enveloped

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10
Q

shape of flavivirus capsid?

A

icosahedral

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11
Q

size of flavivirus capsid?

A

40-60nm diameter

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12
Q

3 characteristics of flavivirus

A
  1. monopartite
  2. linear
  3. 9.6 - 12.3 kb
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13
Q

6 main viruses in flaviviridae family

A
  1. mosquito-borne flavivirus
  2. insect-specific flavivirus
  3. tick-borne flavivirus
  4. NKV flavivirus
  5. hepacivirus
  6. pestivirus
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14
Q

what does NKV mean?

A

no known vector flavivirus

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15
Q

biggest group of flavivirus?

A

mosquito-borne flavivirus

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16
Q

who does Japanese encephalitis affect?

A

Children and immunocompromised adults

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17
Q

who does West Nile encephalitis?

A

Elderly, immunocompromised, and chronically ill patients

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18
Q

what transmits the Japanese Encephalitis Virus?

A

mosquitos –> JEV = arbovirus

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19
Q

2 primary hosts of JEV

A
  1. birds
  2. pigs
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20
Q

1 incidental/dead-end host of JEV

A

Humans

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21
Q

number of JEV cases in humans each year? mortality?

A

30,000 - 50,000 cases in humans each year –> 25-30% mortality

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22
Q

4 symptoms of JEV

A
  1. fever
  2. headache
  3. vomiting
  4. neurologic symptoms
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23
Q

JEV treatment?

A

no treatment –> just supportive care

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24
Q

JEV vaccine?

A

either formalin inactivated or live attenuated

recommended for travel >1 month

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25
describe encephalitis viruses
most are asymptomatic or cause non-specific febrile illness
26
who do encephalitis viruses affect?
children or young adults
27
4 symptoms of severe encephalitis viruses
1. meningoencephalitis 2. aseptic meningitis 3. polio-like acute flaccid paralysis 4. parkinsonian syndrome
28
age-specific incidence of JEV vs WNV
JEV more common in younger age and most people are sero-positive WNV more common in older age and sero-positive is rare
29
what type of mosquito transmits JEV and WNV?
Culex mosquito
30
primary host of WNV?
birds
31
incidental/dead-end host of WNV?
humans + other mammals
32
who does WNV infect?
elderly/immunocompromised ppl
33
6 symptoms of WNV
1. fever 2. headache 3. vomiting 4. muscle weakness 5. lower back pain 6. neurologic symptoms
34
proportion of asymptomatic vs symptomatic cases
80% of cases are asymptomatic 20% of cases are symptomatic and develop into neuroinvasive disease
35
treatment of WNV?
no treatment, not even vaccine
36
how is the spread of WNV measured
regular monitoring of bird sera
37
what type of mosquitos is Dengue Virus transmitted by?
Aedes mosquitos
38
primary host of DENV?
humans
39
8 symptoms of DENV
1. fever 2. headache 3. vomiting 4. abdominal pain 5. low BP 6. tachycardia 7. seizures 8. encephalitis
40
treatment of DENV?
no treatment, not even vaccine
41
5 stages in DENV clinical progression
1. mosquito bite 2. viraemia 3. fever 4. shock hemorrhage 5. antibodies increasingly produced
42
what kills people when they get DENV? % lethality?
Dengue Hemorrhagic Fever/Dengue Shock Syndrome --> 50% lethality
43
how has the distribution of DENV subtypes throughout the world changed over time?
certain subtypes were only in certain areas, but now all 4 genotypes are everywhere
44
what type of mosquitos transmit Zika Virus?
Aedes mosquitos
45
6 symptoms of ZIKV
1. fever 2. maculopapular rash 3. headache 4. joint and muscle pain 5. edema 6. vomiting
46
tropism of ZIKV
nerve cells --> affects myelin
47
recent ZIKV outbreaks lead to: (2)
1. Guillain-Barre syndrome 2. Fetal microcephaly
48
treatment of ZIKV?
No treatment, but working on antibodies and vaccine
49
2 challenges in studying ZIKV in lab
1. no pathogenicity in mice 2. can only grow in vitro if antiviral defenses are removed, but this doesn't give full picture of virus
50
challenge in diagnosing ZIKV
diagnosed thru PCR --> hard in 3rd world country where rapid diagnostics are better
51
describe flavivirus genome organization
5' UTR and cap, structural proteins, non-structural proteins, 3' UTR
52
how many ORF in flavivirus genome?
1 ORF with structural and non-structural regions
53
3 structural proteins
1. C (core) 2. prM/M (membrane) 3. E (envelope glycoprotein)
54
6 non-structural proteins and functions
1. NS1, NS2A, NS4A (RNA replication complex proteins) 2. NS3 (protease/helicase/NTPase) 3. NS4B (membranous web) 4. NS5 (RdRP, guanyltransferase, methyltransferase)
55
what are the only 2 enzymes of flavivirus?
NS3 and NS5
56
relationship btwn NS2A and NS3
NS2A associates with NS3 as cofactor to help cleavage activity
57
why is NS5 a guanyltransferase?
allows G nucleotide to be added at 5' end
58
why is NS5 a methyltransferase?
allows methylation once G is added at 5' end
59
describe an immature flavivirus
upon assembly, has 60 copies of trimer envelope protein
60
describe production of mature flavivirus from immature flavivirus (4 steps)
1. Immature virus is formed in vesicle in transgolgi 2. pH in vesicle changes 3. 60 copies of trimer of envelope protein becomes 90 copies of dimer of envelope protein 4. membrane protein precursor is cleaved by furin, causing structural change into mature
61
describe flavivirus life cycle (6 steps)
1. enters by endocytosis 2. in low pH endosome, fusion proteins exposed to allow virus protein to fuse with endosome envelope 3. +RNA translated into polyprotein 4. polyprotein cleaved by NS3 5. making mature enzymes that make -RNA for replication 6. virus assembles, matures, and is released
62
what residue is crucial on fusion peptides?
Histidine
63
describe how pH changes histidine
histidine has ring where changing conformation of protein
64
how does histidine affect viral entry?
In acidic endosome, His287 and His438 are protonated allowing for fusion protein to change conformation to allow fusion
65
how does histidine affect virus maturation?
In acidic vesicle in trans-golgi, His323 and His146 are protonated to allow change from trimer to dimer for maturation
66
what is the role of furin?
allows maturation of membrane protein
67
what facilitates flavivirus replication?
genome circularization
68
how does genome circularization occur?
5' and 3' ends are brought together by base-pairing (H bonds)
69
how does replication begin?
stem loop A allows RdRP to bind and begin replication, with methylated cap acting as primer
70
flavivirus replication induces ____ and ____
flavivirus replication induces vesicle packets and convoluted membranes
71
where do vesicle packets and convoluted membranes derive from?
from rough-ER
72
what are vesicle packets and convoluted membrane?
sites of replication
73
why do vesicle packets have pores?
exit site for newly synthesized viral RNA
74
describe the assembly of flavivirus
occurs next to pores of vesicle packets --> virions stack within lumen of VP-containing ER network then leave via golgi
75
what is DENV antibody-dependent enhancement?
people who are reinfected get increased severity of infection
76
why does antibody-dependent enhancement occur? 3 results
antibodies from first infection recognize different DENV and allow internalization 1. leukocytes and BBB cells infected 2. inflammation and cytokine storm 3. compromises CNS function