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Virology - Coronavirus
virology
95
Veterinary Medicine
Undergraduate 3
05/31/2012

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Term
genotypeof coronavirus =
Definition
+sense RNA

5'cap,leader squence and poly A tail

Thereofre once released into cytoplasm = ready to be translated
Term
genotypeof coronavirus =
Definition
+sense RNA

5'cap,leader squence and poly A tail

Thereofre once released into cytoplasm = ready to be translated
Term
nucelocapsid of coronavirus =
Definition
helical
Term
ENV of coronavirus
Definition
yes! lipid ENV, host derived
Term
peplomers of caorona virus =
Definition
large club shaped peplomers (made up of glycoproteins) = spike proteins
Term
whats special about corona virus?
Definition
BIGGEST RNA virus
Term
corona virus ORFs =
Definition
many ORFs that cant all be translated directly from genome
Term
initially what ORFs are translated?
Definition
the 2 ORFs closest to the leader sequence
Term
corona virus infects...
Definition
...gut cells, monocytes and neutrophils
Term
entry of corona into host cell -=
Definition
attach to cell via aminopeptidase N on host cell mb = endocytosis.

Then fusion of virus with vesicle = release RNA into cytoplasm
Term
translation uses...
Definition
...one of two alternative start codons at ORF 1 or ORF 2
Term
ORF 1 and 2 code for...
Definition
...polyproteins that are cleaved by viral proteolytic enzymes and assembled into large RNA pol complex
Term
RNA pol makes....
Definition
...-ive RNA - use this as a template from which to make new + copies of the entire virus genome
Term
HOw does the virus translate the rest of the ORFs?
Definition
the viral RNA pol makes a series of nested +ive mRNAs in which the remaining sequences/ORFs are placed next to the leader sequence
Term
how are nested + mRNAs made?
Definition
by copying -ve RNA template from polyU end then dissociating from it = miss out a section and re-associating to complete transcript = leader seq next to ORF that was originally further down the RNA strand
Term
how many proteins do nested + mRNAs code for?
Definition
one or two
Term
advantages of nested + mRNAs/nested transcripts =
Definition
more economical
(can make more of proteins you want without making more of everything else)
Term
nucleoprotein of corona (RNA and capsid synth in...
Definition
...cytoplasm
Term
spike proteins and peplomers are synth in...
Definition
...ER
Term
corona virus gets ENV from...
Definition
...ER (IC budding)
Term
corona is packaged in ....
Definition
...golgi body and then released by exocytosis
Term
advantage of IC budding =
Definition
dont expose peplomers to hosts immunity as soon/b4 exocytosis = delay immune response (gd way to evade immune resposne a bit longer, doesnt cause host cell death by immune response so can live and replicate in host cell for longer)
Term
examples of corna viruses =
Definition
porcine transmissable gastroenteritis (PTGE)
porcine epidemic diarrhoea (PED)
Porine haemagglutinating encephalomyelitis
resp variant of TGE
Bovine coronavirus
canine cornovirus
FCoV & FIP
Term
Porcine transmissable gastroenteritis infection occurs via...
Definition
...ingestion (virus is acid labile but protected by milk or food = allows passage through stomach - resistant to proteolytic enzymes)
Term
Porcine transmissable gastroenteritis infects...
Definition
... intestinal villi in SI (NOT crypts)and macro
Term
hours after Porcine transmissable gastroenteritis virus infection...
Definition
...the entire SI can be infected!! (rapidly cytotoxic)
Term
main result of Porcine transmissable gastroenteritis virus infection =
Definition
diarrhoea = dehydration
Term
what happens if neonates get Porcine transmissable gastroenteritis?
Definition
neonates/piglets express lactase, that breaks down milk,on their enterocytes, destroy enterocytes = milk not broken down = lactose goes to colon = XS lactose in colon = nutrient for enterobacteriacaea such as E. coli =incr in e . coli = inflam and lactose fermentation by bacteria incr osmolarity = enhances diarrhoea

Give neonates Abs to stop bacteria fermenting lactose in colon adding to the problem.
Term
if got Porcine transmissable gastroenteritis may die of
Definition
dehydration
Term
if got Porcine transmissable gastroenteritis and dont die of dehydration...
Definition
...recovery is rapid as crypt cells continue to divide and replaced damaged epi.
Term
coronavirus syndromes recognised in pigs =
Definition
1. TGE
2. porcine epidemic diarrhoea
3. porcine haemagglutinating encephalomyelitis
Term
intro of TGE into a niave herd =
Definition
vom
diarrhoea
fever

throughout herd
Term
morbidity of Porcine transmissable gastroenteritis =
Definition
100% (all pigs in niave herd will be infected)
Term
mortality of Porcine transmissable gastroenteritis =
Definition
near 100% :(

neonates are v susceptible
Term
adults infected with Porcine transmissable gastroenteritis =
Definition
may recover but may become persistantly infected = carriers
Term
ow long is virus secreted for in carriers of Porcine transmissable gastroenteritis ?
Definition
>100days
Term
most common animals see infected with Porcine transmissable gastroenteritis =
Definition
weaned piglets (espec if weaned v young) = post weaning diarrhoea as removed maternal IgA from milk
Term
how is IGA protective against Porcine transmissable gastroenteritis
Definition
binds to virus and inactivates virus attachment
Term
IgG in Porcine transmissable gastroenteritis =
Definition
neutralise virus in vitro but NO protection in vivo
Term
dx of Porcine transmissable gastroenteritis
Definition
immunofluorescence of intestinal tissue at PM
serology
Term
vacc for Porcine transmissable gastroenteritis ?
Definition
no effective vacc :(

nevertheless vacc sow with live attenuated TGE virus to boost maternal immunity
Term
some herds ben able to eradicate Porcine transmissable gastroenteritis by...
Definition
...strict hygeine and removal of sero+ adults
Term
does Porcine transmissable gastroenteritis virus surive well outside host?
Definition
NO! must be carrier - adult with highest Ig levels = carrier and is culled to try and eliminat virus from herd
Term
prevelance of Porcine transmissable gastroenteritis
Definition
rare in UK
Term
preventioin by of Porcine transmissable gastroenteritis by...
Definition
...disinfecting all pens
Term
what is very similar to Porcine transmissable gastroenteritis but less severe (lowere mortalitiy rates)
Definition
porcine epidemic diarrhoea corona virus
Term
if niave herd infected with porcine epidemic diarrhoea (PED) =
Definition
all pigs have diarrhoea
Term
whats more common TGE or PED?
Definition
PED
Term
infection with PED in sows and weaners =
Definition
transient vom and diarrhoea
Term
how do you dx between TGE and PED?
Definition
lab testing - ELISA test on faeces
Term
porcine haemogglutinating encephalitis =
Definition
vom and wasting dz
Term
infection of porcine haemagglutinating encephalomyeltitis infects pigs via....
Definition
...the nasal mucosa and spreads to lungs and SI
Also invades nervous system via vagus and trigeminal nerves
Term
what coronavirus syndrome in pigs DOES NOT cause diarrhoea?
Definition
porcince haemagglutination encephalomyelitis
Term
porcine haemagglutination encephalomyelitis causes...
Definition
...protaracted vom (lasts a long time)
& subsequential weight loss

this is due to infection of distal ganglion of vagus and the vom centre
Term
neurosymptoms or porcine haemagglutinating encephalomyelitis =
Definition
hyperasethesia
paralysis
mm tremors
Term
porcine haemagglutinating encephalomyelitis is very similar to .... (and how are these two differentiated?)
Definition
... porcine polioencephalomyelitis (caused by enterovirus infection)

differentiate between these two via virus isolation and haemagglutination of porcine haemagglutinating enchephalomyelitis virus
Term
resp variant of TGE -=
Definition
serologically the same as TGE but has deletion mutant = lost enterotropism and gained tropism for resp tract
Term
clinical signs of TGE =
Definition
transient cough for 1-2days
Term
resp TGE spreads rapidly through herd via...
Definition
...aerosol (can spread for miles!)

- more rapid than TGE
Term
advantage for pigs becoming infected with resp variant of TGE =
Definition
on recovery seroconvert to TGE = immunity against TGE = by fortunate chance virus has mutated and has self vaccinating :)

because of this TGE has become rare in UK and mainland EU
Term
bovine coronavirus is like...
Definition
...TGE
Term
bovine coronavirus is a major cause of...
Definition
...diarrhoea in calves/yellow scour

(like TGE in piglets)
Term
bovine coronavirus causes what in adult cattles?
Definition
water dysentery/black scours - every cow in herd gets transient diarrhoea for a day or 2

profuse watery dark diarrhoea (may contain blood)
Term
where is bovine corona virus found in the world?
Definition
everywhere! global dz
Term
dx of bovine coronavirus =
Definition
ELISA of faeces
immunofluorescenceof SI
Term
host response to spike protien of bovine coronavirus =
Definition
monoclonal Ab response
Term
bovine corona virus infects...
Definition
...mainly villi = diarrhoea
can infect resp cells and LNs = resp signs
Term
canine coronavirus causes...
Definition
...mild enteritis in puppies (espec post weaned pups)
Term
most strains of canine corona virus =
Definition
low pathogenicity
Term
no epidemic of corona virus in dogs, why?
Definition
probs cus got loadsa low pathogenic strains = act as cover/vacc
Term
2 distinct forms of canine coronavirus =
Definition
enteric and resp form
Term
outbreak of resp form of canine coronavirus =
Definition
severe bronchopneumonia
Term
what incr risk of infection of canine coronavirus?
Definition
young age and stress
Term
enteric canine coronavirus can persist in gut for...
Definition
...months with periodic shedding in faeces with no clinical signs!
Term
FCoV =
Definition
ubiquitous avirulent virus
Term
consequences of FCoV in
a) adult cats
b) kittens
Definition
a) assymptomatic = carrier cats - intermitantly shed virus (can get diarrhoea/be symptomatic)
b) diarrhoea
Term
FCoV infects...
Definition
...colon
Term
risk with perisitant carrier state of FCoV =
Definition
MAY SEROCONVERT TO FIP!
Term
serotype 1 of FCoV =
Definition
receptor used by virus = inknown
most prevelant/common
hard to grow in vitro = hard to study
Term
serotype 2 of FCoV =
Definition
v. similar to canine coronavirus, TGE and bovine coronavirus
Receptor = aminopeptidase N
grows well - can grow in vitro
less common
Term
FIP can evolve from persistant infection with which serotype?
Definition
EITHER!
Term
evolution of FCoV to FIP =
Definition
changes in cell tropism - macrophage tropism
Term
FIP peplomers in...
Definition
...macro golgo body = not exposed on cell surface = IC budding = delay immune response and host cell death
Term
why doesnt infected macro with FIP apoptose?
Definition
FIP interferes with normal cell processes and protects macro from ADCC and NK cells
Term
Immunopathology/cyclical pathology of FIP =
Definition
-infection of macro = incr inflam cytokines by macro = incr bv perm = fluid builds up in peritoneum
-immune response = Thelper cells, antiviral cytotoxic Tcells, neutro and perivascular necrosis
-chemotaxis of macro = incr virus infection of macro
-pyogranulomatous foci containing neutro, lympho, macro, depo of IGG-virusC'3 complexes (activated C' punches cellmbs, even endothelial cells = leaky bvs)
Term
Genetic sequencing of FIP and FCoV
Definition
not found any consistant differences between FIP and FCoV
Term
FIP occurs...
Definition
...sporadically
Term
clinical signs of FIP =
Definition
-vary depending on organs affected
-malaise sickness (due to incr inflam mediators)
-peritonitis, plurisy (inflam of pleura = pain when breathe)
-uvietis (inflam of eye)
-CNS infection and lesions
-vasculitis and oedema
Term
first sign of FIP often =
Definition
uvieitis
Term
dx of FIP
Definition
PM lesions (granulomatous foci=fibrin, leaky bvs, damage coating intestine and peritoneal lesions)
Term
IgGs and Tcells role in FIP =
Definition
tends to make things worse by enhancing macro infection = accelerated pathogenesis
Term
cytotoxic Tcells role in FIP
Definition
may be imp in controlling initial virus infection by removing infected cell b4 persistant stage (viral peptides may be expressed by MHC in the beginning)

Dont yet know what proteins the cytotoxic Tcell would target
Term
vacc for FCoV?
Definition
temp attenuated vacc
Term
admin temp attenuated vacc for FCoV =
Definition
intranasal

need to give annual boosters
Term
in FIP is immunity helpful?
Definition
no ! tends to make things worse!
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