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3. Microbiology, Ecology, and Natural History of Coronaviruses
Pages 137-172

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From page 137...
... Animal coronaviruses tend to follow one of two basic pathogenic models, producing either enteric or respiratory infections. Both models show parallels to the clinical features of SARS patients, the majority of whom presented with respiratory infections but in some cases also suffered from enteric complications.
From page 138...
... Saif Department of Food Animal Health Research Program, Ohio Agricultural Research and Development Center The emergence of severe acute respiratory syndrome (SARS) illustrates that coronaviruses (CoVs)
From page 139...
... , and unlike the other group I CoV, it grows in Vero cells like SARS CoV (Hoffman and Wyler, 1988)
From page 140...
... Thus the likelihood that SARS CoV is a zoonotic infection potentially transmitted from wild animals to humans is not unprecedented based on previous research on interspecies transmission of animal CoV and wildlife reservoirs for CoV. As examples, the porcine CoV, TGEV, and canine and feline CoVs can cross-infect pigs, dogs, and cats with variable disease expression and levels of cross-protection in the heterologous host (Saif and Wesley, 1999; Saif and Heckert, 1990)
From page 141...
... 141 glands CNS, kidney? b salivary Other Vitremia Systemic Systemic Hepatitis, systemic Eye, CNS Kidney, oviduct Viremia, Subclinical?
From page 142...
... Pathogenesis of Animal Enteric and Respiratory Coronaviruses Pathogenesis of Group I TGEV and PRCV CoV: Models of Enteric and Respiratory Infections Because both pneumonia and diarrhea occur in SARS patients, an understanding of the tissue tropisms and pathogenesis of respiratory and enteric animal CoVs should contribute to our understanding of similar parameters for SARS. The TGEV targets the small intestinal epithelial cells leading to severe villous atrophy, malabsorptive diarrhea, and a potentially fatal gastroenteritis (Table 3-1)
From page 143...
... BCoV causes three distinct clinical syndromes in cattle: calf diarrhea; winter dysentery with hemorrhagic diarrhea in adults; and respiratory infections in cattle of various ages, including cattle with shipping fever (Table 3-1) (Clark, 1993; Lathrop et al., 2000a; Lathrop et al., 2000b; Saif and Heckert, 1990; Storz et al., 1996, 2000a, Tsunemitsu et al., 1995)
From page 144...
... . Shipping Fever BCoV Infections More recent studies done in 1995 have implicated BCoV in association with respiratory disease (shipping fever)
From page 145...
... by enhancing virus transmission. Impact of Respiratory Co-Infections on CoV Infections, Disease, and Shedding Shipping fever is recognized as a multifactorial, polymicrobial respiratory disease complex in young adult feedlot cattle with several factors exacerbating respiratory disease, including BCoV infections (Lathrop et al., 2000a,b; Storz et al., 1996; Storz et al., 2000a; Storz et al., 2000b)
From page 146...
... . By analogy, hospital procedures that could potentially generate aerosols or exposure to higher initial doses of SARS CoV may enhance SARS transmission or lead to enhanced respiratory disease (Kamps and Hoffman, 2003a,b)
From page 147...
... leading to immune suppression may trigger FIP in chronically infected cats, similar to its role in shipping fever CoV infections of cattle. Two major forms of FIP occur: (1)
From page 148...
... Group III CoVs: Infectious Bronchitis Virus (IBV) : Model for Respiratory CoV Infection with Other Target Tissues The IBV is a highly contagious respiratory disease of chickens, like SARS, spread by aerosol or possibly fecal-oral transmission, and distributed worldwide (Cavanagh and Naqi, 2003; Cook and Mockett, 1995)
From page 149...
... Department of Pediatrics, Department of Microbiology & Immunology, Elizabeth B Lamb Center for Pediatric Research, Vanderbilt University Medical Center, Nashville, TN For coronavirus investigators, the recognition of a new coronavirus as the cause of severe acute respiratory syndrome (SARS)
From page 150...
... Finally, areas of need for research in coronavirus replication, genetics, and pathogenesis will be summarized. Coronavirus Life Cycle The best studied model for coronavirus replication and pathogenesis has been the group 2 murine coronavirus, mouse hepatitis virus, and much of what is known of the stages of the coronavirus life cycle has been determined in animals and in culture using this virus.
From page 151...
... . The next discrete stage in the life cycle is translation and proteolytic processing of viral replicase proteins from the input genome RNA, followed by formation of cytoplasmic replication complexes in association with cellular membranes (Denison et al., 1999; Gosert et al., 2002; Shi et al., 1999; van der Meer et al., 1999)
From page 152...
... Replicase gene proteins likely mediate positive-strand, negative-strand, subgenomic, and genomic RNA synthesis, as well as processes of capping, polyadenylation, RNA unwinding, template switching during viral RNA synthesis, and discontinuous transcription and transcription attenuation. The coronavirus replicase polyproteins and mature replicase proteins represent the largest and most diverse repertoire of known and predicted distinct enzymatic functions of any positive-strand RNA virus family.
From page 153...
... . Because of the parallel evolution of the proteinases, their cleavage sites, and the hierarchical cleavage processes, the proteolytic processing of the coronavirus replicase proteins may serve as distinct regulatory and genetic elements (Ziebuhr et al., 2001)
From page 154...
... . Taking advantage of naturally high rates of homologous RNA-RNA recombination and of host range determinants in the S protein, the development of targeted recombination has allowed more defined and detailed studies of the accessory and structural genes of MHV, transmissible gastroenteritis virus (TGEV)
From page 155...
... . In addition, we have engineered mutations in the MHV replicase gene to define the requirements for polyprotein processing and to determine the role of specific replicase proteins in replication in culture and in pathogenesis in animals.
From page 156...
... . Similarly, understanding of replicase gene expression, processing, and predicted functions has identified possible targets for structure/function studies and possible therapeutic intervention.
From page 157...
... is the etiological agent of severe acute respiratory syndrome (SARS)
From page 158...
... The detection of SCoV-like viruses in small, live wild mammals in a retail market indicates a route of interspecies transmission, although the natural reservoir is not known. Severe acute respiratory syndrome (SARS)
From page 159...
... for the N gene of the human SCoV. Swabs from four of six Himalayan palm civets were positive in the RT-PCR assay (see Table 3-2)
From page 160...
... 6. Sera from five animals had neutralizing antibody to the animal coronavirus; these were from three palm civets, a raccoon dog, and a Chinese ferret badger, respectively (see Table 3-2)
From page 161...
... TABLE 3-3 Prevalence of Antibody to Animal SCoV SZ16 in Humans. Controls Are Serum Specimens from Patients Hospitalized for Nonrespiratory Diseases in Guangdong Made Anonymous Occupation Sample numbers Antibody positive (%)
From page 162...
... Most of these differences were found in the S gene coding region. The existence of the additional 29-nt sequence in the animal viruses results in demolishing the open reading frames (ORFs)
From page 163...
... When the S-gene sequences of the four animal viruses were compared with 11 human SCoV viruses, 38 nucleotide polymorphisms were noted, and 26 of them were nonsynonymous changes (see Table 3-4)
From page 164...
... 164 T T T T T T T T T T T T GT G G G A AC AC A A A A A A A A T T T T T T T T T T T T C T C C C C C C deletion. T T CG C TTTT C CG CG CG CGT CGT CGT CGT CGT CGT CGT CGT cleotide G G G A A A A A A A A A A nu CG C C C TA C C C C C C C a G G G G G GC GC GC T T T T T T T T T T indicates G G G AC AC AC AC AC AC AC AC AC AC AC CGT C T C C C C C C C C C C C C Dash T T T T C C C C C C C C C C C bold.
From page 165...
... 2003. Severe acute respiratory syndrome (SARS)
From page 166...
... 2003. Genomic characterisation of the severe acute respiratory syndrome coronavirus of Amoy Gardens out break in Hong Kong.
From page 167...
... 2003. Identification of a novel coronavirus in patients with severe acute respiratory syndrome.
From page 168...
... 2003. A novel coronavirus associated with severe acute respiratory syndrome.
From page 169...
... 2003. A major outbreak of severe acute respiratory syndrome in Hong Kong.
From page 170...
... 2003. Characterization of a novel coronavirus associ ated with severe acute respiratory syndrome.
From page 171...
... 2003. A cluster of cases of severe acute respiratory syndrome in Hong Kong.
From page 172...
... 2003. Epidemiology and cause of severe acute respiratory syndrome (SARS)


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