Download What Factors Exacerbate Porcine Respiratory Coronavirus

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

Rinderpest wikipedia , lookup

Diarrhea wikipedia , lookup

Sexually transmitted infection wikipedia , lookup

Oesophagostomum wikipedia , lookup

Leptospirosis wikipedia , lookup

African trypanosomiasis wikipedia , lookup

Dirofilaria immitis wikipedia , lookup

Sarcocystis wikipedia , lookup

Hepatitis C wikipedia , lookup

Swine influenza wikipedia , lookup

Influenza A virus wikipedia , lookup

Trichinosis wikipedia , lookup

Schistosomiasis wikipedia , lookup

HIV wikipedia , lookup

Human cytomegalovirus wikipedia , lookup

Chickenpox wikipedia , lookup

Ebola virus disease wikipedia , lookup

Orthohantavirus wikipedia , lookup

Traveler's diarrhea wikipedia , lookup

Norovirus wikipedia , lookup

Coccidioidomycosis wikipedia , lookup

West Nile fever wikipedia , lookup

Neonatal infection wikipedia , lookup

Hospital-acquired infection wikipedia , lookup

Antiviral drug wikipedia , lookup

Gastroenteritis wikipedia , lookup

Hepatitis B wikipedia , lookup

Pandemic wikipedia , lookup

Marburg virus disease wikipedia , lookup

Herpes simplex virus wikipedia , lookup

Lymphocytic choriomeningitis wikipedia , lookup

Henipavirus wikipedia , lookup

Middle East respiratory syndrome wikipedia , lookup

Transcript
ANIMAL CORONAVIRUSES:
LESSONS FOR SARS
Linda J. Saif
TGEV
Saif ©
BCoV
Food Animal Health Research Program,
Ohio Agricultural Research and Development Center,
Department of Veterinary Preventive Medicine,
The Ohio State University, Wooster, Ohio 44691, USA
Saif ©
Coronavirus Genetic Groups, Target Tissues and Diseases
Genetic Group
I
Virus
Host
Disease/ Infection Site
Respiratory
Enteric
Other
HCoV-229E
TGEV
PRCoV
PEDV
FIPV
FCoV
CCoV
HCoV-OC43
MHV
RCoV
HEV
BCoV**
human
pig
pig
pig
cat
cat
dog
human
mouse
rat
pig
cattle
X
(x)
X
III
IBV
TCoV
chicken
turkey
X
X
X
Kidney, Oviduct
IV ??
SARS
human
X
X?
Kidney?
II
X
X
X
X
X
X
X
X
??
X
X
Systemic
CNS, Systemic
Eye, GU
CNS
SARS Transmission
Droplets -
close contacts
• Households
• Hospitals (Health cares workers)
• “Superspreaders”
Airborne ?
Fecal/oral ?
Fomites ?
Masked Palm Civets
Animal host:
• Civet Cat - Reports from Hong Kong suggest masked palm civet cat may be
an animal host for SARS (Guan et al, Science Express, Sept 4, 2003)
Susceptible animal models:
• Cynomolgus macaque- (Fouchier et al, Nature 2003. 423:240)
• Pigs- Canadian report negative, but 5-6 week-old pigs used and TGEV/PRCV
serostatus undefined
• Avian species- USDA reported no transmission to SPF chickens, turkeys,
ducks or quail
Porcine Coronaviruses
Group I
PRCV
Saif ©
TGEV
Saif ©
Enteric Infections
TGEV : Transmissible Gastroenteritis Virus (1965)
Infect all age groups but highest mortality in baby pigs
PEDV : Porcine Epidemic Diarrhea Virus (1978, Europe; 1980’s, Asia) EpidemicHigh mortality in baby pigs
Endemic - Older pigs (>3 months) infected
Respiratory Infections
PRCV : Porcine Respiratory Coronavirus (1986, Europe; 1989, USA)
S gene deletion mutant of TGEV (621 – 682 bp near the N-terminus)
Infect all age groups - 1- 3-month-old, most disease
There are 2 models for respiratory and
enteric coronaviruses in animals
PRCV is a S gene deletion mutant of TGEV (same serotype)
◆TGEV infects small intestinal villous enterocytes;
Intestine
occasionally upper respiratory tract
Induces villous atrophy leading to vomiting and
diarrhea which are the main clinical signs
Lung
◆PRCV infects epithelial cells of the upper and lower
respiratory tract and a few unidentified cells in the small
intestine
Moderate or subclinical respiratory disease occurs,
but interstitial pneumonia is evident in most pigs
TGEV MILLER
Summary of genetic analysis of S gene deletion area and ORF3/3a, 3-1/3b of TGEV
and PRCV strains (Kim et al 2000)
Four Clinical Syndromes Occur
with BCoV Infections
Enteric Infections
Calf diarrhea
Diarrhea, dehydration
 Intestinal villous atrophy
Winter dysentery
Bloody diarrhea + upper
respiratory infection
 Intestinal villous atrophy
Respiratory Infections
Calf respiratory disease
Bovine respiratory disease
complex (shipping fever)
Target Age Groups
Birth to 4 wks of age
6 months to adult
2 wks to 6 months
6-9-month-old
feedlot cattle
Cough, nasolacrimal discharge, pneumonia
All BCoV isolates belong to 1 serotype (2 subtypes) and are pneumoenteric
Only point mutations occur in the S gene of BCoV-E vs BCoV-R strains
Which tissues do coronaviruses infect?
Coronavirus
Infected
Tissues
Macaque a
SARS
Pigs
TGEV-V TGEV-A (vaccine)
Cattle
PRCV
PEDV
BCoV-E
BCoV-R
Viremia
NT
-
-
+
-
NT
NT
Upper
Resp.Tract
+
+
++
++
-
+
++
Lower
Resp. Tract
+
+/-
+
+++
-
+
+++
Intestine
+/1/4
+++
+
+/-
++
(colon)
++
(colon)
++
(colon)
Intact
Pt mutations b
Deletion
Intact
(nt 214 and 655)
(621-682 nt)
S-gene
a
Fouchier, et al 2003
b
Ballesteros et al, 1997
Pt mutations c
(42 aa changes at 38 sites)
c Hasoksuz,
et al 2002
How do respiratory coronavirus infections in
animals compare to those in humans?
Respiratory Coronaviruses
Clinical signs:
Cells infected:
Lesions/
Pathology:
PRCV
Cough
± Nasolacrimal discharge
+ Fever
± Pneumonia
.
Nares, Trachea,
Alveoli, Bronchi
Alveolar macrophages
Interstitial pneumonia
Duration of shedding:
Nasal
3-10 days
Fecal
Variable, 0-a few days
BCoV-R
Cough
Nasolacrimal discharge
+ Fever
± Pneumonia
Nasal turbinates
Trachea
Bronchi, Alveoli
Interstitial emphysema
Bronchiolitis, alveolitis
5-10 days (17 days)
4-8 days (17 days)
What Factors Exacerbate Respiratory Coronavirus
Infections or Virus Shedding?
1. Aerosols
 Higher virus titers, longer shedding and more severe
respiratory disease (Van Cott et al, 1993)
2. Dose
 Higher dose = higher titer, longer shedding (Van Cott et
al, 1993)
• Pigs given 108.5 TCID50 had more severe pneumonia and
deaths than pigs exposed by contact (Jabrane et al, 1994)
3. Concurrent or sequential respiratory viral infections
 Porcine arterivirus (PRRSV) first, then PRCV after 5 days
(Hayes et al, 2000)
• Longer shedding of PRCV after dual infection
• Fecal shedding of PRCV, mainly after dual infection
• Prolonged fever, respiratory disease and reduced weight
gain after dual infection
 PRCV first, then Swine Influenza Virus 2 days later (Van
Reeth and Pensaert, 1994)
• Enhanced respiratory disease
Pig Lung tissue
Control
PRCV
PRRSV  PRCV
What Factors Exacerbate Porcine Respiratory Coronavirus
Infections or Virus Shedding?
4. Pigs infected with the Arterivirus, PRRSV or with PRCV followed by
bacterial LPS in 5 days developed more severe respiratory disease upon
LPS exposure and enhanced fever compared to pigs inoculated with each
agent alone (Laborque et al, 2002; Van Reeth et al, 2002)
5.Treatment with immunosuppressive agents: the synthetic corticosteroid,
dexamethasone
Enhanced the severity of TGEV infections (Shimizu and Shimizu, 1979)
In 1 of 4 cows inoculated with WD-BCoV-E, treatment also induced a
recurrence of fecal BCoV shedding (Tsunemitsu et al, 1999)
What Factors Exacerbate Respiratory Bovine
Coronavirus Infections or Virus Shedding?
1. Calves with lower serum Ab titers (VN titer <
400) to BCoV were more likely to be infected
and develop disease
2. Stress of shipping cattle to feedlots
3. Co-mingling cattle from different farms
4. Other concurrent respiratory infections (viruses
and bacteria)
Infectious Bronchitis Virus (IBV)
Pathogenesis
 Primary site of infection is upper respiratory tract
 Trachea and Bronchi
Virus detection
 Viremia
 Nasal secretions
 Feces and Urine
 Disease is most severe in baby chicks
Other organs infected (sites of IBV persistence with periodic nasal shedding)
 Kidneys (Nephropathogenic strains) Tissue tropism of one IBV strain altered from
respiratory to kidney tissues by serial passage in the cloaca (Uenaka et al 1998)
 Oviducts
 Intestine
Feline Infectious Peritonitis Virus(FIPV)
Pathogenesis
 Primary sites of infection are the pharyngeal, respiratory or intestinal epithelial
cells
 Two major forms:
 Effusive- peritoneal fluid accumulation
 Non effusive –fever, CNS involvement
 Viremia occurs due to infection of monocytes
 Virus is distributed throughout the body in macrophages
 Lesions: pyogranulomas with thrombosis
After antibody development: fulminant disease with
1) Immune complexes with complement, in sera and ascites fluids
2) Antibody dependent enhancement of infection
Do coronaviruses cross the species barrier?
Example: Oral inoculation of calves with enteric coronaviruses from
captive wild ruminants
Enteric coronavirus
origin:
Sambar Deer White-tailed Deer Waterbuck
Calf inoculation
Diarrhea:
Fecal shedding:
Seroconversion to BCV:
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Conclusion: Coronaviruses from wild ruminants can experimentally
infect young calves (Tsunemitsu, et al 1995)
Wild ruminants
Cattle transmission ?
Do coronaviruses cross the species barrier?
Example: Oral inoculation of poultry with BCoV-E
Turkey poults
Diarrhea:
Yes
Fecal shedding:
Yes (12 DPI)
Seroconversion to BCoV:
Yes
Chicks
No
No
NT
Conclusion: Bovine coronavirus can experimentally infect baby
turkeys (Ismail et al, 2001)
Cattle
Bird transmission ?
EMERGING ZOONOTIC VIRAL INFECTIONS

It is estimated that 75% of emerging human pathogens are zoonotic
(Murphy et al,1998 Taylor et al 2001) and that 61% of all human pathogens are
zoonotic (Woolhouse et al, 2002).

Zoonotic pathogens that infect both domestic and wildlife hosts and have
a broad host range, appear most likely to emerge (Cleaveland et al, 2001).

RNA viruses are more likely to be zoonotic than DNA viruses
(Morse,1997;Woolhouse et al, 2002).
Viral RNA replicases lack proofreading functions leading to high
mutation rates with more rapid evolution
Quasispecies exist allowing plasticity within the viral population for
adaptation to new hosts
Zoonotic RNA virus examples: Influenza, Nipah, Hendra, Rift Valley
Fever Virus, West Nile Virus, HIV, SARS CoV(?)
FACTORS INFLUENCING VIRAL EMERGENCE
Introduction of virus into a new host
“Virus traffic” via ecologic changes, demographic changes, human
activity/behavior (Lederberg et al,1992, Morse et al, 1997)
Enhanced host susceptibility (immunosuppression, preexisting health
conditions, malnutrition, poilymicrobial coinfections, etc)
Establishment and dissemination within the new host population
Increase in host movements (global travel, rural to urban migration),
density, allow for greater spread
Increasing numbers of infected individuals increase opportunity for
transmissible variants to arise
Human activity may disseminate vectors or reservoir
CONTROL OF EMERGING/ZOONOTIC
INFECTIONS
 Effective global disease surveillance and coordination of efforts
 Multidisciplinary research efforts and teams to investigate disease
outbreaks
 For zoonotic diseases, the combined efforts of biomedical and veterinary
scientists are essential, but few mechanisms currently exist to support
this type of collaboration and cooperation
CONCLUDING REMARKS
 Enteric coronaviruses alone can cause fatal infections in seronegative young
animals; respiratory coronavirus infections are more often fatal in adults
when combined with other factors (shipping fever in cattle)
 Factors that exacerbate respiratory coronavirus infections in animals include
high exposure doses, respiratory coinfections (viruses, LPS), treatment with
corticosteroids
 Knowledge of SARS pathogenesis (using appropriate animal models) is
extremely important to design effective vaccines
 There are no vaccines to prevent respiratory coronavirus infections except
for IBV infections in chickens
 Vaccination for IBV (killed or live) is complicated by the existence of multiple
serotypes/subtypes
 Only short-term protection is needed because of the short life span of chickens
REFERENCES
Ballesteros, M.L., C.M. Sanchez, L. Enjuanes. 1997. Two amino acid changes at the N-terminal of the transmissible gastroenteritis
coronavirus pike protein result in the loss of enteric tropism. Virology 227:378-388.
Cavanagh, D., and S.A. Naqi. 2003. Infectious Bronchitis. In Diseases of Swine (Y.M. Saif et al., eds) 11th Ed. Iowa State Press, Ames,
Iowa.
Cho, K.O., A. Hoet, S.C. Loerch, T.E. Wittum and L.J. Saif. 2001. Evaluation of concurrent shedding of bovine coronavirus via the
respiratory and enteric route in feedlot cattle. Am. J. Vet. Res. 62:1436-1441.
Cho, K.O., P.R. Nielsen, K.O. Chang, S. Lathrop and L.J. Saif. 2001. Cross-protection studies of respiratory, calf diarrhea and winter
dysentery coronavirus strains in calves and RT-PCR and nested PCR for their detection. Arch. Virol. 146:2401-2419.
El-Kanawati, Z. R., H. Tsunemitsu, D. R. Smith and L. J. Saif. 1996. Infection and cross-protection studies of winter dysentery and calf
diarrhea bovine coronavirus strains in colostrum-deprived and gnotobiotic calves. Am. J. Vet. Res. 57:48-53.
Fouchier, R.A.M., T. Kuiken, M. Schutten, G. van Amerongen, G.J.J. van Doornum, B.G. van den Hoogen, M. Peiris, W. Lim, K. Stohr,
A.D.M.E. Osterhaus. 2003. Koch postulates fulfilled for SARS virus. Nature 423:240.
Guan,Y, et al. 2003. Isolation and characterization of viruses related to the SARS coronavirus from animals in Southern China. Science
Express, Sept 4,2003
Hasoksuz, M., S. Sreevatsan, K.O. Cho, A.E. Hoet and L.J. Saif. 2002. Molecular analysis of the S1 subunit of the spike glycoprotein of
respiratory and enteric bovine coronavirus isolates. Virus Res. 84:101-109.
Hayes, J., K. Sestak, G. Myers, L. Kim, P. Stromberg, B. Byrum, R. Mohan, and L.J. Saif. Evaluation of dual infection of nursery pigs
with U.S. strains of porcine reproductive and respiratory syndrome virus and porcine respiratory coronavirus. Proc. VIIth International
Symposium on Nidoviruses (Corona and Arteriviruses), Lake Harmony, PA, May 20-25, 2000.
Ismail, M.M., K.O Cho, L.A. Ward, L.J. Saif and Y.M. Saif. 2001. Experimental bovine coronavirus in turkey poults and young chickens.
Avian Dis. 45:157-163.
Jabrane, A., C. Girard, Y. Elazhary. 1994. Pathogenicity of porcine respiratory coronavirus isolated in Quebec. Can. Vet. J. 35:86-92.
REFERENCES
Kim, L., J. Hayes, P. Lewis, A.V. Parwani, K.O. Chang and L.J. Saif. 2000. Molecular characterization and pathogenesis of transmissible
gastroenteritis coronavirus (TGEV) and porcine respiratory coronavirus (PRCV) field isolates co-circulating in a swine herd. Arch.
Virol. 145:1133-1147.
Lathrop, S.L., T.E. Wittum, S.C. Loerch, L.J. Perino and L.J. Saif. 2000. Antibody titers against bovine coronavirus and shedding of the
virus via the respiratory tract in feedlot cattle. Am. J. Vet. Res. 61:1057-1061.
Labarque, G., K. Van Reeth, S. Van Gucht, H. Nauwynck, M. Pensaert. 2002. Porcine reproductive-respiratory syndrome virus infection
predisposes pigs for respiratory signs upon exposure to bacterial lipopolysaccharide. Vet. Microbiol. 88:1-12.
Laude, H., K.V. Reeth, M. Pensaert. 1993. Porcine respiratory coronavirus: molecular features and virus-host interactions. Vet. Res.
24:125-150.
Lederberg, J., R.E. Shope, S.C. Oaks. 1992. Emerging infections—Microbial threats to health in the US. Institute of Medicine, National
Academies Press.
Morse,S.S. 1997. The public health threat of emerging viral disease. Am Soc Nutr Sci. 127:951S-957S.
Olsen, C.W. 1993. A review of feline infectious peritonitis virus: molecular biology, immunopathogenesis, clinical aspects, and
vaccination. Vet. Microbiol. 36:1-37.
Pensaert, M.B. 1999. Porcine Epidemic Diarrhea. In Diseases of Swine 8th Ed. (Straw, B.E., et al., eds) Iowa State Univ. Press. Ames, IA,
pp 179-185.
Saif, L. J. and Heckert, R. A. 1990. Enteric coronaviruses. In Viral Diarrheas of Man and Animals, (L. J. Saif and K. W. Theil, eds), CRC
Press, Boca Raton, Florida, pp. 185-252.
Saif, L. J. and R. Wesley. 1999. Transmissible gastroenteritis virus. In Diseases of Swine (B. Straw et al., eds) 8th Ed. Iowa State Univ.
Press, Ames, Iowa.
Saif, L.J. 2002. Coronaviruses: Update on diagnosis, pathogenesis and control of bovine coronavirus-associated calf diarrhea, winter
dysentery and shipping fever. Proc. Iowa Veterinary Medical Association Mtg., Iowa State University, College of Veterinary Medicine,
Ames, IA, September 12, 2002.
Sestak, K., R.K. Meister, J.R. Hayes, L. Kim, P.A. Lewis, G. Myers and L.J. Saif. 1999. Active immunity and T-cell populations in pigs
intraperitoneally inoculated with baculovirus-expressed transmissible gastroenteritis virus structural proteins. Vet. Immunol.
Immunopath.70:203-21.
REFERENCES
Sestak, K. and L.J. Saif. 2002. Porcine coronaviruses. In Trends in Emerging Viral Infections of Swine (J.J. Zimmerman, et al,
eds.) Iowa State Univ. Press, Ames, Iowa (In press).
Shimizu, M. and Y. Shimizu. 1979. Effects of ambient temperatures on clinical and immune responses of pigs infected with
transmissible gastroenteritis virus. Vet. Microbiol. 4:109-116.
Shoup, D. I., D. J. Jackwood, and L. J. Saif. 1997. Active and passive immune responses to transmissible gastroenteritis virus
(TGEV) in swine inoculated with recombinant baculovirus-expressed TGEV spike (S) glycoprotein vaccines. Am. J. Vet. Res.
58:242-250.
Tsunemitsu, H., H. Reed, Z. El-Kanawati, D. Smith, and L. J. Saif. 1995. Isolation of coronaviruses antigenically
indistinguishable from bovine coronavirus from a Sambar and white tailed deer and waterbuck with diarrhea. J. Clin.
Microbiol. 33:3264-3269.
Tsunemitsu, H., Z. El-Kanawati, D. Smith, H. Reed, and L. J. Saif. 1995. Isolation of coronaviruses antigenically
indistinguishable from bovine coronavirus from wild ruminants with diarrhea. J. Clin. Microbiol. 33:3264-3269
Van Cott, J. L., T. A. Brim, R. A. Simkins and L. J. Saif. 1993. Antibody-secreting cells to transmissible gastroenteritis virus
and porcine respiratory coronavirus in gut- and bronchus-associated lymphoid tissues of neonatal pigs. J. Immunol.
150:3990-4000.
Van Cott, J., T. Brim, J. Lunney, and L. J. Saif. 1994. Contribution of antibody secreting cells induced in mucosal lymphoid
tissues of pigs inoculated with respiratory or enteric strains of coronavirus to immunity against enteric coronavirus
challenge. J. Immunol. 152:3980-3990.
Van Reeth, K. and M. Pensaert. 1994. Porcine respiratory coronavirus-medicated interference against influenza virus
replication in the respiratory tract of feeder pigs. Am. J. Vet. Res. 55:1275-1281.
Van Reeth, K., S. Van Gucht and M. Pensaert. 2002. In vivo studies on cytokine involvement during acute viral respiratory disease of
swine: troublesome but rewarding. Vet. Immunol. Immunopath. 87:161-168.
Woolhouse, M.E.J. 2002. Population biology of emerging and re-emerging pathogens. Trends in Microbiol. 10: S3-S7