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Virology-flaviridae
viruses
94
Veterinary Medicine
Undergraduate 3
05/31/2012

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Term
flaviridae =
Definition
yellow fever
Term
2 main geni of flaviridae=
Definition
flavirus
pestivirus
Term
flaviridae genome =
Definition
+ssRNA

with 5'cap, no poly A tail and short hair pin loop protecting RNA from degradation
Term
nucelocapsid of flaviridae =
Definition
icosahedral
Term
flaviridae ENV?
Definition
yes! tightly fitting with small peplomers
Term
replication of flaviridae is similar to...
Definition
...FMD and calicivirus
Term
flaviridae infection of host cell =
Definition
endocytosis after binding to sialic acid, derc endosome pH = fusion of virus ENV and endosome mb = release + ssRNA into cytoplasm
Term
ORFs in flaviridae =
Definition
single polycistronic ORF translated inot one large polyprotein thats then cleaved into lots of diff proteins
Term
structural genes in flaviridae virus grouped at ____ end
Definition
5' end
Term
translation of flaviridae mRNA is via...
Definition
...host cells ribosomes of the RER
Term
leader sequence of flaviridae acts as a secretory signal to...
Definition
...ensure proteins become inserted onto ER mb
Term
structural flaviridae proteins are processed by...
Definition
...host proteases
Term
NSP are at ____ end and =
Definition
3'end

protease and RNA pol
Term
virus assmebles and buds from...
Definition
...ER
Term
flaviridae exits the cell bia...
Definition
...exocytosis only
Term
flavivirus main example =
Definition
louping ill virus
Term
Rs of louping ill virus =
Definition
sialic acid/gangliosides (found on variety of cells including nerves)
Term
louping ill virus has dsRNA intermediates =
Definition
potentially gd IFN inducers
Term
louping ill virus is a member of the....
Definition
...tick borne encephalitis group of flavirus
Term
louing ill vector =
Definition
ixodes ricinus tick (found upland areas where sheep graze)
Term
what kind of transmission of loupig ill virus do you get between ticks?
Definition
transdadial transmission
Term
motality of red grouse infected with louping ill virus =
Definition
80%

this is imp as red grouse is an economically imp gaming bird
Term
louping ill virus infects what sp?
Definition
not sp restricted. Infects a variety of mammals and birds
Term
louping ill virus is mainly seen in...
Definition
...sheep in spring or autumn (when you have peak levels of ticks)
Term
louping ill virus replicates in...
Definition
...leucocytes
macro
dendritic cells
endothelial cells 9therefore can infect BBB and get into brain!)
Term
tick saliva helps viral infection by...
Definition
...supressing hosts immunity
Term
get primary fever with louping ill virus associated with...
Definition
...IFN response and viraemia spread of virus
Term
viraemia of louping ill virus is...
Definition
...prolonged and can allow spread to CNS = neuro signs
Term
neuro signs seen with louping ill virus infection =
Definition
ataxia
mm tremors and spasms
louping (abnormal gait)
paralysis
death
Term
neurone louping ill virus infection =
Definition
nerve cell death
Term
reservoir hosts of louping ill virus =
Definition
red grouse
voles
hares
Term
route of louping ill virus infection in red grouse =
Definition
red grouse eat infected ticks
Term
more severe dz with louping ill virus is asociated with...
Definition
...immunosupression due to coinfection with ehrlicia phagocytophillia (a small bacteria = IC parasite)

ehrlichia phagocytophillia is ynergistic with louping ill virus
Term
after infection with louping ill virus and recovered =
Definition
immune (rise in Ab titre)
Term
if ewes properly immunised will you see louping ill virus in lambs?
Definition
no as lambs protected by maternal Abs
Term
vacc of louping ill virus ?
Definition
inactivated cell culture derived vacc and used to protect breeding ewes - annual boosters
Term
mst sheep with louping ill virus ten to be between the gae of...
Definition
...6months-2yrs
Term
dx of louping ill virus =
Definition
1. virus isolation
2. serology - IgM rise = infection is now, IgG rise = may be infection now, last wk or incr IgG due to sheep being vacc, therefore need to to serology quickly)
3. immunohistology
Term
name 3 pestiviruses
Definition
swine fever
border dz
BVDV
Term
BVDV prevelance =
Definition
common, and world wide
Term
one of the most imp pathogenic viruses of cattle in UK =
Definition
BVDV
Term
do all cattle with BVDV show signs of dz?
Definition
only a proportion of cows in herd (the runts) show signs of dz
Term
does BVDV cause diarrhoea?
Definition
raerly!
Term
genotype of BVDV =
Definition
+ssRNA

like FMD has IRES (Internal Ribosomal entry site) to initiate transcription
Term
structural genes of BVDV at ____ end of +ssRNA
Definition
5'
Term
structural genes of BVDV are translocated to...
Definition
...ER mb whre theyre cleaved into their seperate parts by host signal peptodase/host proteases
Term
viral NSP2/3 of BVDV do what?
Definition
cleave key proteins that cause pathogenesis
Term
BVDV leaves cell by...
Definition
...exocytosis only
Term
dz seen with BVDV is due to...
Definition
...conversion to cytopathic strain due to NSP3 mutation, in chronic infection Usually mutation into 80kD NSP3 ( a bigger NSP3)
Term
normal activity of NSP3 of BVDV=
Definition
proteolytic action restricted to at ER = not much damage to host cell
Term
mutation of BVDV NSP3 =
Definition
proteolytic activity of NSP3 isnt restricted to around ER so it drifts around host cell breaking proteins up!
Term
does BVDV cause an IFN response?
Definition
normal BVDV blocks IFN response, however cytopathic mutated BVDV does induce IFN response
Term
BVDV R =
Definition
CD46 (C' control protein)

protein on the surface of many cells
Term
why  is BVDV only seen in cattle?
Definition
CD46 (R BVDV binds to) are diff in diff sp
Term
2 biotypes of BVDV. which one is most common in UK?
Definition
biotype 1
Term
conversion of BVDV biotype 1 to ctopathic form causes...
Definition
...'typical' mucosal dz
Term
conversion of BVDV biotype 2 to cytopathic form cuases...
Definition
...thrombocytopaenia (decr platelets) and haemorrhagic dz - haemorrhagic diarrhea or haemorrhage of mucous mb
Term
BVDV can cause many dzs, such as...
Definition
1. acute infection of susceptible cattle with non-cytopathic BVDV
2.moderate/severe outbreaks with cytopathic BVDV
3. infection of preg cow with non-cytopathic BVDV
4. endemic herds
5. mucosal dz (cytopathic biotype 1)
Term
infection of BVDV via...
Definition
...nasal or oral route
Term
BVDV replicates in
Definition
epi cells eg tonsil epi
Term
BVDV spreads in body via...
Definition
...viraemia
Term
BVDV is found in what cells?
Definition
T and Bcells and also causes a decr in the no of t and b cells, BVDV is immunosupressive = get secondary infection = exacerbate resp dz
Term
dz is usually mild woth non-cytopathic virus. morbidity is...
Definition
...high
Term
clinical signs of non-cytopathic BVDV =
Definition
few if any!

transient fever, then Ab response to birus and recover)
Term
why dont you ever find cytopathic BVDV on its own in cattle?
Definition
as cytopathic BVDV has mutated from non-cytopathic BVDV
Term
clincial signs of cytopathic BVDV =
Definition
fever
depression
diarrrhoea
erosions in mouth and coronary band (petechiae)
some deaths
immunosupressive = secondary infection = exacerbate resp dz
Term
animals that recover from BVDV ...
Definition
...seroconvert (have gd immunity/high Ab levels against BVDV)
Term
infection of preg cow in 1st 30days of gestation =
Definition
transplacental infection of fetus =

-early embryonic death :(
-cow mounts an immune response and wont get BVDV again - 2nd preg fine :)
Term
BVDV infection of preg cow 30-90 days into gestation =
Definition
transplacental infection of fetus =

-embryonic death/fetal death = abortion or mummification :(
-cow mounts immune response-2nd preg will be fine :)
Term
BVDV infection of preg cow 90-120 days into gestation =
Definition
transplacental infection of fetus =

-infection during critical period of calves immune system develoment. Calf survives but is immunotolerant to BVDV = lifelong persistance of BVDV infection in calf with no immune respnse and may not have clincial signs = carrier
-cow mounts immune response, clears virus and becomes immune
Term
infection of preg cow >125days into gestation=
Definition
transplacental infection of fetus =

cow and claf develop immune response as calf has a developed immune system.
calf will reach full term but can get some fetal defects:
-retinal dysplasia
-cerebellar hypoplasia
-cerebral cavitation
-low birth weight
-neonatal death :(
Term
once got endemic of BVD in herd =
Definition
hard to eradicate :( (due to persistant infections)
Term
how common in BVDV infection in adults?
Definition
rare as got high immunity once been infected once
Term
what age of cow most likely to become infected with BVDV?
Definition
heifers when first joining the herd (ie during 2nd preg)
Term
how mainy animals in endemic herd are perisitantly infected?
Definition
approx 1% - maintains infection and low fertility levels
Term
mutation of biotype 1 BVDV NSP3 to...
Definition
...80kD NSP3 that has tropism for mucosal immune system eg peyers patches, lamina propria, mesenteric LNs
Term
onset of mucosal BVDV dz =
Definition
may be acute or gradual
Term
BVDV mucosal dz can be seen at any age but most commonly seen...
Definition
...between 6months and 2yrs
Term
clinical signs of BVDV mucosal dz =
Definition
1. pyrexia
2. anorexia
3. profuse watery diarrhoea (DDx = johnes) - wont go away = progressive dz
4. nasal discharge
5. erosive stomatitis- inflam of mouth mucous mb and ulcers around mouth, nose, oesoph and forestomachs
6. dehydration
7. emaciation
8. foot lesions
9. hyperaemia
10. intestinal necrosis of peyers patches and lymphoid tissue = kills all lymphocytes in peyers patch
Term
mortality of BVDV mucosal dz =
Definition
100%

usually takes several wks and then die
Term
mortality of BVDV mucosal dz =
Definition
100%

usually takes several wks and then die
Term
how can you differentiate between BVDV and FMD?
Definition
FMD will have a few cows affected

BVDV will have one cow affected with chronic onset
Term
how many cows are sero+?
Definition
approx 80%

most likely to be healthy and maintained immunity from previous infection
Term
immunotolerant persistantly infected cows Ab levels =
Definition
NO Abs = sero-

therefore serology ELISA of individual cows Ab levels is of limited us for dx of BVDV
Term
how can you ID infected herd?
Definition
Abs in milk
Term
dx of BVDV =
Definition
-tissue culture + immunofluorescence
-detection of BVDV RNA by RT-PCR
-Ag capture ELISA = coat plate with Abs that capture the virus, + virus, + another Ab with marker that detects virus. Use to find persistant immunotolerant carriers
Term
control of BVDV to get BVDV free herd =
Definition
test and cull (use Ag capturee ELISA test)
Term
BVDV effect on herd =
Definition
big impact on productivity and fertlitly of the herd :(
Term
BVDV vacc?
Definition
yes, live attenuated and inactivated vacc but...
-not all totally effective
-may not protect against all strains of BVDV
-not certain to prevent fetal infection
-some evidence may contribute to dz onset in tolerant animals (as how can you have a live attenuated virus of a non-cytopathic virus???) - better now as engineered virus to remove what causes IFN block from virus
-can spread virus by using same dirty needles (need to wash inbetween, can get self washing needles!)
Term
can kill ENV virus with...
Definition
...detergent (easy)
Term
2 step BVDV Vacc of remaining animals after test and cull =
Definition
1st admin inactivated vacc, then 2nd booster dose admin live attenuated vacc
Term
replacemtn animals need to be vacc against BVDV at...
Definition
...6months old
Term
biosecurity is v imp and effective in control of BVDV as...
Definition
...BVDV is an ENV virus and Env viurses are so easily destroyed with detergent!
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