lec 22 dengue and zika

Question 1

dengue and zika are in the ____ family

Answer 1

flavivirus

Question 2

flaviviruses are ______

Answer 2

+ssRNA

Question 3

what determines serotype?

Answer 3

if there the immune system can neutralize it. Is not genetically determined. There is also genetic variation among each serotype

Question 4

The dengue genome has ____ ORF and _____ cleaves the polyprotein into ___ proteins

Answer 4

one;
host protease;
10

Question 5

the structural proteins are _____

Answer 5

in/on the viral particle

Question 6

describe dengue NS1, 3, and 5

Answer 6

3 and 5 are RNA pol and helicase
NS1 is mysterious, but secreted in large amounts, thought to have to do with immune evasion/disease progression

Question 7

History of dengue distribution

Answer 7

1950s-80s Aedes eradicated from South/Central America
HUGE outbreak after this
movement following WWII from East Asia

Question 8

___% of dengue cases are subclinical

Answer 8

60

Question 9

how many dengue cases per year?
Hemorrhagic fever?
Deaths?

Answer 9

50 to 100 million
720,000 are DHF
24,000 deaths

Question 10

most severe cases occur in ____ people

Answer 10

older

Question 11

Symptoms of Dengue Fever

Answer 11

high fever
headache
retroorbital pain
myalgias/athralgias
Fatigue
*GI - nausea/vomiting (signals complications)
cutaneous rash
hemorrhagic manifestations (low platelet count, also reduces volume of blood -> more concentrated blood -> shock)
thrmobocytopenia

Question 12

DHF/DSS symptoms

Answer 12

increased vascular permeability -> causes severe disease
hemoconcentration
hypovolemic shock (heart doesnt pump properly)
hemorrhagic manifestations
thrombocytopenia
abdominal pain
cytokine storm

Question 13

dengue symptom timeline

Answer 13

days 1-3 high fever and high viral load
days 4-6 immune system kicks in, low viral load/fever, decreased platelets, high hematocrit (increased permeability, potential chance of shock)

Question 14

Integral Hypothesis of Dengue

Answer 14

Individual risk factors, viral risk factors, and epidemiological risk factors affect the manifestation of the disease

Question 15

Main theories of Dengue pathology

Answer 15

1. antibody dependent enhancement (ADE)
2. T cell altered peptide ligand mediated cytokine storm (original antigenic sin - OAS)
3. host genetics (innate and adaptive response)
4. dengue virulence (viral genetic factors)

Question 16

Support for ADE

Answer 16

neonates have Dengue at 6-8 months, and 2-3 years due to maternal antibodies being in the area between neutralization and enhancement

Question 17

How does original antigenic sin play into Dengue pathology?

Answer 17

changing an outer peptide ligand can induce a response that produces cytokines but does not control the virus

Question 18

ADE concept

Answer 18

the primary infection is asymptomatic or mild
the secondary infection from the same strain is protected but from a different serotype is actually more severe

Multiple antibodies can block binding of virions to cell receptor (neutralize)
Few antibodies (or low affinity) can enhance uptake of virions in cells with Fcgamma receptor (immune cells)

Question 19

There is a gray area in which ______ is negative and _______ is positive

Answer 19

neutralization
enhancement

Question 20

There is a relationship between pre-disease antibody titer and disease outcome. _______ titer is associated with severe disease

Answer 20

intermediate

Question 21

Primary infection of dengue leads to (increased/reduced) risk for DENV1-4

Answer 21

1: reduced
2: increased
3: increased and reduced (this strain is very pathogenic as is)
4: increased risk
zika: reduced risk

Question 22

Complement factors are also correlated with Dengue severity through what mechanisms

Answer 22

NS1 can cleave complement
Activates MBL, properdin, C4a, C3a, C5a, C5-C9 MAC, CFD
inhibits C1-INH, CFH (inhibitors of complement)

Question 23

Sanofi vaccine

Answer 23

reverse genetics of yellow fever vaccine, replace Envelope and membrane to Dengue serotypes
This vaccine is only effective in those with previous Dengue infection since it does not activate T cell response

Question 24

CDC-inviragen vaccine

Answer 24

Dengue 2 attenuated virus with each serotypes membrane/envelope protein
perfect for DENV2, ok for 1, doesn’t work for 3, unknown for 4

Question 25

NIH vaccine

Answer 25

all full genome but DENV2 is env/mem in DENV4 genome
deletes portion of genome that allows the genome to circularize which allows RNA pol to go around and around
good with 1, not so good with 2

Question 26

Zika genome description

Answer 26

1 ORF
polyprotein cleaved into 10 proteins

Question 27

Zika was isolated from _______ in ______

Answer 27

Rhesus monkey in Zika forest

Question 28

At first Zika did not cause disease, but cases of _____ were seen which caused alarm. Zika was found in the _____

Answer 28

microcephaly
CSF

Question 29

When Zika became a problem, cases of ____ became more mild

Answer 29

dengue

Question 30

Zika pathogenesis

Answer 30

brain
eye
body fluids (spread sexually)
placenta
testis
uterus and vagina

Question 31

How does primary infection of zika affect risk of Dengue secondary infection?

Answer 31

1: no increased risk
2: increased risk
3: increased risk
4: increased risk
zika: reduced risk