Molecular Evolution Analysis and Geographic Investigation of Severe Acute Respiratory Syndrome Coronavirus-Like Virus in Palm Civets at an Animal Market and on Farms

Kan, Biao; Wang, Ming; Jing, Huaiqi; Xu, Huifang; Jiang, Xingran; Yan, Mei; Liang, Weili; Zheng, Han; Wan, Kanglin; Liu, Qiyong; Cui, Buyun; Xu, Yun; Zhang, Enmin; Wang, Hongxia; Ye, Jingrong; Li, Guichang; Li, Machao; Cui, Zhigang; Qi, Xiaobao; Chen, Kai; Du, Lanying; Gao, Kai; Zhao, Yunlong; Zou, Xiao Zhong; Feng, Yue Ju; Gao, Yu; Hai, Rong; Yu, Dongzhen; Guan, Yi; Xu, Jianguo

doi:10.1128/jvi.79.18.11892-11900.2005

Cited by 311 publications

(328 citation statements)

References 30 publications

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“…Phylogenetic analysis, coupled with serological and epidemiological studies, has implicated Himalayan palm civets as a probable source for zoonotic transmission of SARS-CoV to humans (13,23). However, recent studies showing a limited distribution of SARS-CoV in wild animals as well as the observation that palm civets show relevant clinical signs after experimental infection with SARS-CoV (61) make these animals an unlikely reservoir.…”

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confidence: 99%

“…Comparative analyses of the SARS-CoV genomes of different isolates from both humans and animals throughout the different phases of the epidemic showed a high rate of evolution in the viral attachment protein, the spike (S) glycoprotein that was critical for the transition from animal-to-human to human-to-human transmission (7,23,42,53). The S glycoprotein binds to the receptor angiotensin-converting enzyme 2 (ACE-2), mediating viral entry and establishing host range (30,32).…”

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confidence: 99%

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Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice

Rockx

Sheahan

Donaldson

et al. 2007

J Virol

108

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The severe acute respiratory syndrome (SARS) epidemic was characterized by high mortality rates in the elderly. The molecular mechanisms that govern enhanced susceptibility of elderly populations are not known, and robust animal models are needed that recapitulate the increased pathogenic phenotype noted with increasing age. Using synthetic biology and reverse genetics, we describe the construction of a panel of isogenic SARS coronavirus (SARS-CoV) strains bearing variant spike glycoproteins that are representative of zoonotic strains found in palm civets and raccoon dogs, as well as isolates spanning the early, middle, and late phases of the SARS-CoV epidemic. The recombinant viruses replicated efficiently in cell culture and demonstrated variable sensitivities to neutralization with antibodies. The human but not the zoonotic variants replicated efficiently in human airway epithelial cultures, supporting earlier hypotheses that zoonotic isolates are less pathogenic in humans but can evolve into highly pathogenic strains. All viruses replicated efficiently, but none produced clinical disease or death in young animals. In contrast, severe clinical disease, diffuse alveolar damage, hyaline membrane formation, alveolitis, and death were noted in 12-month-old mice inoculated with the palm civet HC/SZ/61/03 strain or early-human-phase GZ02 variants but not with related middle-and late-phase epidemic or raccoon dog strains. This panel of SARS-CoV recombinants bearing zoonotic and human epidemic spike glycoproteins will provide heterologous challenge models for testing vaccine efficacy against zoonotic reintroductions as well as provide the appropriate model system for elucidating the complex virus-host interactions that contribute to more-severe and fatal SARS-CoV disease and acute respiratory distress in the elderly.

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confidence: 99%

mentioning

confidence: 99%

Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice

Rockx

Sheahan

Donaldson

et al. 2007

J Virol

108

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“…The rapid identification of highly similar viruses in masked palm civet and racoon dog in the live-animal markets provided strong evidence of an animal origin of SARS-CoV and played an important role in the prevention of further outbreaks (Guan et al, 2003). However, subsequent epidemiological studies on civets from market, farm and wild populations demonstrated that there was no widespread infection among wild or farmed civets, implying that wild animal(s) other than civets may serve as the natural reservoir(s) of SARS-CoV (Tu et al, 2004;Kan et al, 2005;Poon et al, 2005).Recently, we and another independent group have simultaneously reported the detection of SARS-like coronavirus (SL-CoV) or SARS coronavirus-like virus in different horseshoe bat species in the genus Rhinolophus, providing evidence that suggests bats as a natural reservoir of this group of viruses (Lau et al, 2005;Li et al, 2005b). Due to the close genetic and antigenic relationship of SARS-CoVs and SL-CoVs, this group of viruses has been named the SARS cluster coronaviruses or group 2b coronavirus (G2b-CoV) in differentiation from other group 2 coronaviruses in the genus Coronavirus (Gorbalenya et al, 2004;Lau et al, 2005;Li et al, 2005b;Woo et al, 2006).…”

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confidence: 99%

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confidence: 99%

Full-length genome sequences of two SARS-like coronaviruses in horseshoe bats and genetic variation analysis

Ren

et al. 2006

Journal of General Virology

110

118

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Bats were recently identified as natural reservoirs of SARS-like coronavirus (SL-CoV) or SARS coronavirus-like virus. These viruses, together with SARS coronaviruses (SARS-CoV) isolated from human and palm civet, form a distinctive cluster within the group 2 coronaviruses of the genus Coronavirus, tentatively named group 2b (G2b). In this study, complete genome sequences of two additional group 2b coronaviruses (G2b-CoVs) were determined from horseshoe bat Rhinolophus ferrumequinum (G2b-CoV Rf1) and Rhinolophus macrotis (G2b-CoV Rm1). The bat G2b-CoV isolates have an identical genome organization and share an overall genome sequence identity of 88-92 % among themselves and between them and the human/civet isolates. The most variable regions are located in the genes encoding nsp3, ORF3a, spike protein and ORF8 when bat and human/civet G2b-CoV isolates are compared. Genetic analysis demonstrated that a diverse G2b-CoV population exists in the bat habitat and has evolved from a common ancestor of SARS-CoV.Severe acute respiratory syndrome (SARS) is one of the most important emerging zoonotic diseases in the 21st century. A novel coronavirus, the SARS coronavirus (SARS-CoV), was identified as the aetiological agent of SARS (Fouchier et al., 2003;Ksiazek et al., 2003;Marra et al., 2003;Peiris et al., 2003;Rota et al., 2003;Zhong et al., 2003). The rapid identification of highly similar viruses in masked palm civet and racoon dog in the live-animal markets provided strong evidence of an animal origin of SARS-CoV and played an important role in the prevention of further outbreaks (Guan et al., 2003). However, subsequent epidemiological studies on civets from market, farm and wild populations demonstrated that there was no widespread infection among wild or farmed civets, implying that wild animal(s) other than civets may serve as the natural reservoir(s) of SARS-CoV (Tu et al., 2004;Kan et al., 2005;Poon et al., 2005).Recently, we and another independent group have simultaneously reported the detection of SARS-like coronavirus (SL-CoV) or SARS coronavirus-like virus in different horseshoe bat species in the genus Rhinolophus, providing evidence that suggests bats as a natural reservoir of this group of viruses (Lau et al., 2005;Li et al., 2005b). Due to the close genetic and antigenic relationship of SARS-CoVs and SL-CoVs, this group of viruses has been named the SARS cluster coronaviruses or group 2b coronavirus (G2b-CoV) in differentiation from other group 2 coronaviruses in the genus Coronavirus (Gorbalenya et al., 2004;Lau et al., 2005;Li et al., 2005b;Woo et al., 2006). Molecular and serological studies indicated that at least five different horseshoe bat species in mainland China and Hong Kong harbour G2b-CoVs. They include Rhinolophus sinicus, Rhinolophus pearsonii, Rhinolophus ferrumequinum, Rhinolophus macrotis and Rhinolophus pusillus. Full-length genome sequences were published for three isolates, one from R. pearsonii (Rp3) and two from R. sinicus (HKU3-1 and HKU3-2). The sequences of the HKU3-1 and HKU3-2 ...

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“…The increase in virulence after passage in a new host is, at least partly, explained by the usage of new, otherwise low-functioning receptors. Thus far, mutations in the spike proteins of MHV-JHMV, HCoV-OC43 and SARS-CoV were reported to cause adaptation to a new animal species (Phillips et al, 2002;Butler et al, 2006;Kan et al, 2005). However, recent studies have shown that other viral proteins such as haemagglutinin-esterase, nucleocapsid and integral membrane proteins are involved in efficient replication in animals (Iacono et al, 2006;Roberts et al, 2007).…”

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confidence: 99%

Neuropathogenesis of a mouse-adapted porcine epidemic diarrhea virus infection in suckling mice

Kotani

Shirato

Nagata

et al. 2013

Journal of General Virology

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A mouse-adapted porcine epidemic diarrhea virus, MK-p10, showed higher neurovirulence in suckling mice than a non-adapted MK strain. There was no difference in virus growth, whereas clear differences between these two virus infections existed in the type of target cells infected, the spread of virus and the cytokine levels produced in the brain. In the early phase of infection, neurons, astrocytes and neural progenitor cells were infected by MK-p10, whereas neural progenitor cells were the only target cells infected by MK. On days 4-5 post-inoculation, MK-p10 antigens were distributed in a number of neurons in a wide area of the brain; however, antigens were restricted in MK infection. In moribund mice in both infection groups, viral antigens were found in a wide area of the brain. The wide spectrum of initial target cells following MK-p10 infection, as well as its faster spread in the brain, may be evidence of enhanced virulence in suckling mice.Porcine epidemic diarrhea virus (PEDV) is an enveloped alphacoronavirus with a single-stranded, positive-sense RNA genome of about 30 kb and is a causative agent for diarrhoea in pigs. It induces mild intestinal disease in adult pigs, whereas it causes lethal diarrhoea in piglets (Pensaert & de Bouck, 1978). However, the pathogenesis of diseases caused by PEDV is not well understood, since there are no animal models available for the study of infection.We have recently obtained a PEDV strain adapted to suckling mice (Shirato et al., 2010). Although the neurovirulence of PEDV has not been described thus far in pigs, we reported the establishment of a highly neurovirulent strain of PEDV via adaptation of a celladapted MK strain (Kusanagi et al., 1992) to the mouse brain (Shirato et al., 2010). MK showed weak neurovirulence when injected into a suckling mouse brain, whereas MK-p10 showed increased neurovirulence. When inoculated with MK-p10 via the oral route, mice showed slight weight loss with no other clinical symptoms, but no viral antigen or histological changes were observed in the intestine. In this study, we investigated the enhanced neuropathological features of the MK-p10 strain compared with those of the MK strain in suckling mice by histopathological and immunochemical analysis. Our study suggests that the alteration of the cell tropism in the suckling mouse brain, as well as the faster spread of the virus to a variety of cells, mainly neurons, leads to higher neurovirulence in the adapted MK-p10 strain.MK and MK-p10 were prepared as previously reported (Shirato et al., 2010). Pregnant BALB/c mice were obtained from Japan SLC and Sankyo Labo Service Corporation, and newborn mice were inoculated intracerebrally with 10 ml containing ca 10 4 p.f.u. virus solution. Those mice were clinically observed and their brains were histologically or immunohistochemically examined. Kaplan-Meier analysis was used for statistics, and P,0.05 was considered to be statistically significant. Animal experiments were approved by the Committees on Experimental Animals, National Inst...

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Molecular Evolution Analysis and Geographic Investigation of Severe Acute Respiratory Syndrome Coronavirus-Like Virus in Palm Civets at an Animal Market and on Farms

Cited by 311 publications

References 30 publications

Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice

Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice

Full-length genome sequences of two SARS-like coronaviruses in horseshoe bats and genetic variation analysis

Neuropathogenesis of a mouse-adapted porcine epidemic diarrhea virus infection in suckling mice

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