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Subject:
From:
Sukie Crandall <[log in to unmask]>
Date:
Tue, 30 Dec 2008 10:12:12 -0500
Content-Type:
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ECE is a known and genetically identified coronavirus. Work has been
done on that original coronavirus in the AFIP and in Michigan State.

Yes, of course, it has spread to naive populations. Heck, that is how
it spread in the beginning. That is common for viral spread, and, yes,
it has always been a virus that easily spread to healthy ferrets. Much
of its original spread was through ferrets so robust that they were
appearing in ferret shows.

The very rare mutant of ECE which looks like FIP (Feline Infectious
Peritonitis) in behavior had scattered reports for a few years before
finally specimens were gotten, with the first description from a
Spanish and German team (and then shortly after specimens here in the
U.S. and French specimens as well). In the U.S. the original specimens
sent for study were in the N.W. but since there pretty rapidly were
specimens elsewhere in the U.S. it's not known if that was a point of
entry or if there simply was an alert enough vet (Dr. Katrina Ramsell).
Here's a little piece of history on that for you: I was the one who
got the German and Spanish team and the vets in the U.S. together with
Dr. Matti Kiupel's team at Michigan State and talking with Dr. Bruce
Williams at the AFIP so that specimens from multiple locations could be
studied and compared, and people and places could each do what they do
best. That happened just because I noticed the European description in
the literature and because I chat periodically about unusual diseases
with multiple vets, including those individuals. What began simply as
a coincidence of communication and reading worked out well for rapid
increase in knowledge to help on more than one continent.

ECE itself appears to have originated as a mutant of a mink coronavirus
in a fur farm in the U.S. which bred for mink and for fitch (ferret
fur).

The current mystery disease might be a mutant of ECE or might be a
different virus. The disease appears to respond well to Tamiflu, a
med which greatly reduces viral replication.

Specimens have been sent to Michigan State since it is one of the few
places in the world which can analyze coronaviruses throughly enough
to tell types of coronaviruses apart.

There are simpler tests which can tell if a coronavirus is present,
but not which one. (That caused some problems with at least one SARS
studies at first, BTW, because SARS is a different type of coronavirus
and not all human medical research facilities realized there are other
coronaviruses like ECE and FIP. So -- surprise -- some human health
researchers in the Netherlands described ECE damage in ferrets and FIP
damage in cats before they learned that they had not managed casual
infection in ferrets and cats, but instead had some animals who already
had ECE and FIP. Now, human coronavirus researchers first do the
general coronavirus test to make sure their animal models don't already
have their own types of coronavirus. )

There is hope that having the genetic material can eventually lead to
easier testing and even perhaps to vaccinations.

What you've been thinking about ECE is way off the mark. Here is a
primer:

http://www.afip.org/consultation/vetpath/ferrets/ECE/ECE.html

and here are some journal article abstracts on ECE and on the earlier
identified ECE mutant that behaves like FIP behaves:

BEGIN MULTIPLE QUOTED ABSTRACTS (some articles have no abstracts)

Coronavirus-associated epizootic catarrhal enteritis in ferrets.
Williams BH, Kiupel M, West KH, Raymond JT, Grant CK, Glickman LT.
Department of Veterinary Pathology, Armed Forces Institute of
Pathology, Washington, DC 20306-6000, USA.

OBJECTIVE: To characterize clinical signs and lesions and identify
the etiologic agent associated with epizootic catarrhal enteritis in
domestic ferrets.
DESIGN: Cross-sectional study.
ANIMALS: 119 ferrets with epizootic diarrhea of presumed viral cause
and 5 control ferrets. 
PROCEDURE: Clinical records and biopsy or necropsy specimens of
ferrets with presumed epizootic catarrhal enteritis were reviewed.
Immunohistochemical staining for coronavirus antigen was performed on
paraffin-embedded tissues from approximately 10% of affected ferrets
to identify viral antigen and determine its distribution. Transmission
electron microscopy was performed on fecal samples and sections of
jejunum. Virus isolation studies as well as immunofluorescent tests
for other similar viruses were performed.
RESULTS: Characteristic microscopic lesions consistent with intestinal
coronavirus infection (vacuolar degeneration and necrosis of villus
enterocytes; villus atrophy, fusion, and blunting; and lymphocytic
enteritis) were consistently detected in affected ferrets. Coronavirus
particles were identified in feces and jejunal enterocytes by use of
transmission electron microscopy. Immunohistochemical staining of
jejunal sections revealed coronavirus antigens. Antigen staining was
not detected in healthy ferrets or ferrets with other gastrointestinal
tract diseases. Virus isolation was unsuccessful, and other similar
viruses were not detected.
CONCLUSIONS AND CLINICAL RELEVANCE: Results strongly implicate a
coronavirus as the causative agent of epizootic catarrhal enteritis
in ferrets. Diagnosis may be made on the basis of a combination of
historical, clinical, and microscopic findings.

Virology. 2006 May 25;349(1):164-74. Epub 2006 Feb 24.
Molecular characterization of a novel coronavirus associated with
epizootic catarrhal enteritis (ECE) in ferrets.
Wise AG, Kiupel M, Maes RK.
Diagnostic Center for Population and Animal Health, Lansing, MI 48909,
USA. [log in to unmask]

A novel coronavirus, designated as ferret enteric coronavirus (FECV),
was identified in feces of domestic ferrets clinically diagnosed with
epizootic catarrhal enteritis (ECE). Initially, partial sequences of
the polymerase, spike, membrane protein, and nucleocapsid genes were
generated using coronavirus consensus PCR assays. Subsequently, the
complete sequences of the nucleocapsid gene and the last two open
reading frames at the 3' terminus of the FECV genome were obtained.
Phylogenetic analyses based on predicted partial amino acid sequences
of the polymerase, spike, and membrane proteins, and full sequence of
the nucleocapsid protein showed that FECV is genetically most closely
related to group 1 coronaviruses. FECV is more similar to feline
coronavirus, porcine transmissible gastroenteritis virus, and canine
coronavirus than to porcine epidemic diarrhea virus and human
coronavirus 229E. Molecular data presented in this study provide the
first genetic evidence for a new coronavirus associated with clinical
cases of ECE.

Vet Rec. 2006 Apr 15;158(15):523.
Detection of feline infectious peritonitis virus-like antigen in
ferrets.
Martinez J, Ramis AJ, Reinacher M, Perpinan D.

J Comp Pathol. 2008 Jan;138(1):54-8. Epub 2007 Dec 11.
Identification of group 1 coronavirus antigen in multisystemic
granulomatous lesions in ferrets (Mustela putorius furo).
Martinez J, Reinacher M, Perpinan D, Ramis A.
Departament de Sanitat i Anatomia Animals, Facultat de Veterinaria,
Universitat Aut˜noma de Barcelona, Barcelona, Spain.
[log in to unmask]

Tissues from nine ferrets with granulomatous lesions similar to those
seen in feline infectious peritonitis were examined histopathologically
and immunohistochemically. Four main types of lesions were observed:
diffuse granulomatous inflammation on serosal surfaces; granulomas
with areas of necrosis; granulomas without necrosis; and granulomas
with neutrophils. Other less commonly seen lesions were granulomatous
necrotizing vasculitis and endogenous lipid pneumonia. FCV3-70
monoclonal antibody produced immunolabelling of group 1 coronavirus
antigen in tissue samples from eight animals, the antigen being present
in the cytoplasm of macrophages in the different types of granulomatous
lesions.

Vet Rec. 2008 Feb 9;162(6):180-4.
Clinical aspects of systemic granulomatous inflammatory syndrome in
ferrets (Mustela putorius furo).
Perpinan D, Lopez C.
Nine ferrets (Mustela putorius furo) were diagnosed with systemic
granulomatous inflammatory syndrome between 2005 and 2006. Common
signs included diarrhoea, lethargy, weight loss, and weakness in
the hindlimbs. Pathological findings consisted of mesenteric
lymphadenopathy, splenomegaly, hypergammaglobulinaemia and non-
regenerative anaemia. The condition was progressive and fatal in
all the cases.

Vet Pathol. 2008 Mar;45(2):236-46.
Erratum in:Vet Pathol. 2008 Jul;45(4):598.
Clinicopathologic features of a systemic coronavirus-associated disease
resembling feline infectious peritonitis in the domestic ferret
(Mustela putorius).
Garner MM, Ramsell K, Morera N, Juan-Salles C, JimŽnez J, Ardiaca M,
Montesinos A, Teifke JP, Lohr CV, Evermann JF, Baszler TV, Nordhausen
RW, Wise AG, Maes RK, Kiupel M.
From 2002 to 2007, 23 ferrets from Europe and the United States were
diagnosed with systemic pyogranulomatous inflammation resembling feline
infectious peritonitis (FIP). The average age at the time of diagnosis
was 11 months. The disease was progressive in all cases, and average
duration of clinical illness was 67 days. Common clinical findings were
anorexia, weight loss, diarrhea, and large, palpable intra-abdominal
masses; less frequent findings included hind limb paresis, central
nervous system signs, vomiting, and dyspnea. Frequent hematologic
findings were mild anemia, thrombocytopenia, and
hypergammaglobulinemia. Grossly, whitish nodules were found in numerous
tissues, most frequently the mesenteric adipose tissue and lymph nodes,
visceral peritoneum, liver, kidneys, spleen, and lungs. One ferret
had a serous abdominal effusion. Microscopically, pyogranulomatous
inflammation involved especially the visceral peritoneum, mesenteric
adipose tissue, liver, lungs, kidneys, lymph nodes, spleen, pancreas,
adrenal glands, and/or blood vessels. Immunohistochemically, all
cases were positive for coronavirus antigen using monoclonal antibody
FIPV3-70. Electron microscopic examination of inflammatory lesions
identified particles with coronavirus morphology in the cytoplasm of
macrophages. Partial sequencing of the coronavirus spike gene obtained
from frozen tissue indicates that the virus is related to ferret
enteric coronavirus.

END MULTIPLE QUOTED ABSTRACTS

[Posted in FML 6199]


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