The Group-Specific Murine Coronavirus Genes Are Not Essential, but Their Deletion, by Reverse Genetics, Is Attenuating in the Natural Host

Haan, Cornelis A. M. de; Masters, Paul S.; Shen, Xiaolan; Weiss, Susan R.; Rottier, Peter J. M.

doi:10.1006/viro.2002.1412

Cited by 218 publications

(286 citation statements)

References 45 publications

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“…Further refinement of the nonhuman primate model, coupled with a full-length cDNA clone for the introduction of precise modifications into rescued icSARS-CoV, should allow for the development of candidate vaccines for the clinic. For example, deletion of the nonconserved, group-specific ORFs encoded within the last one-third of the genome was not detrimental CoV replication in vitro, but viruses were attenuated in vivo (22,28,29). These ORFs can also be replaced with foreign genes, providing for heterologous gene expression from recombinant viruses and from single-hit replicon particles (22,30,31).…”

Section: Discussionmentioning

confidence: 99%

“…RT-PCR of Leader-Containing Transcripts. Leader-containing amplicons were obtained from WT and icSARS-CoV-infected cells by using primers at the 3Ј end of the genome (5Ј-tttttttttttttttttttttgtcattctcctaagaagc 29710 -3Ј) or in the X5 or X3 ORFs (5Ј-ttaattaattaatttgttcgtttatttaaaacaaca 28091Ј -3Ј, 5Ј-ttaattaattatggataatctaactccataggttct 27238 -3Ј) and in the SARS leader RNA sequence at the 5Ј end of the genome (5Ј-aaagccaaccaacctcgatc-3Ј; nucleotides [26][27][28][29][30][31][32][33][34][35]. Leader-containing amplicons were subcloned into TopoII vectors and sequenced.…”

Section: Methodsmentioning

confidence: 99%

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Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus

Yount

Curtis

Fritz

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

350

400

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus

Yount

Curtis

Fritz

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

350

400

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“…Shen et al [89] and Youn et al [104] have also demonstrated that proteins 3b and 5a, respectively, are not required for replication in vitro. Deletion of all the non-gene 1 non-structural protein genes of MHV produced virus that replicated in mice but which, unlike the wild-type virus, was non-lethal [33].…”

Section: Role Of Other Coronavirus Proteins In Pathogenicitymentioning

confidence: 99%

Coronavirus avian infectious bronchitis virus

2007

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-Infectious bronchitis virus (IBV), the coronavirus of the chicken (Gallus gallus), is one of the foremost causes of economic loss within the poultry industry, affecting the performance of both meat-type and egg-laying birds. The virus replicates not only in the epithelium of upper and lower respiratory tract tissues, but also in many tissues along the alimentary tract and elsewhere e.g. kidney, oviduct and testes. It can be detected in both respiratory and faecal material. There is increasing evidence that IBV can infect species of bird other than the chicken. Interestingly breeds of chicken vary with respect to the severity of infection with IBV, which may be related to the immune response. Probably the major reason for the high profile of IBV is the existence of a very large number of serotypes. Both live and inactivated IB vaccines are used extensively, the latter requiring priming by the former. Their effectiveness is diminished by poor cross-protection. The nature of the protective immune response to IBV is poorly understood. What is known is that the surface spike protein, indeed the amino-terminal S1 half, is sufficient to induce good protective immunity. There is increasing evidence that only a few amino acid differences amongst S proteins are sufficient to have a detrimental impact on cross-protection. Experimental vector IB vaccines and genetically manipulated IBVs -with heterologous spike protein genes -have produced promising results, including in the context of in ovo vaccination.

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“…1b and 1c), indicating that additional factors (such as sequence elements, RNA structures, proteins) are involved in regulating the relative abundance of viral mRNAs. It is tempting to speculate that the transcription mechanism used by coronaviruses, arteriviruses and (in part) toroviruses (van Vliet et al, 2002) has evolved to allow the production of a large set of structural and nonstructural (some of them probably virulence-associated) proteins (de Haan et al, 2002), whose abundance can be regulated at the transcriptional level. Regulation of coronavirus gene expression can be even further extended by the presence of additional, downstream ORFs in the 59 unique regions of some of the subgenomic mRNAs.…”

Section: Subgenomic Mrna Synthesismentioning

confidence: 99%

Mechanisms and enzymes involved in SARS coronavirus genome expression

Thiel

Иванов

Putics

et al. 2003

Journal of General Virology

815

960

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A novel coronavirus is the causative agent of the current epidemic of severe acute respiratory syndrome (SARS). Coronaviruses are exceptionally large RNA viruses and employ complex regulatory mechanisms to express their genomes. Here, we determined the sequence of SARS coronavirus (SARS-CoV), isolate Frankfurt 1, and characterized key RNA elements and protein functions involved in viral genome expression. Important regulatory mechanisms, such as the (discontinuous) synthesis of eight subgenomic mRNAs, ribosomal frameshifting and posttranslational proteolytic processing, were addressed. Activities of three SARS coronavirus enzymes, the helicase and two cysteine proteinases, which are known to be critically involved in replication, transcription and/or post-translational polyprotein processing, were characterized. The availability of recombinant forms of key replicative enzymes of SARS coronavirus should pave the way for high-throughput screening approaches to identify candidate inhibitors in compound libraries. INTRODUCTIONSevere acute respiratory syndrome (SARS) is a lifethreatening form of pneumonia (Peiris et al., 2003a). In the course of a few months in 2003, an epidemic emerged that has spread from its likely origin in Guangdong Province, China, to 32 countries. By 11 June 2003 more than 8400 cases and 789 deaths had been recorded by the World Health Organization. The rapid transmission by aerosols (and probably also the faecal-oral route) and the high mortality rate make SARS a global threat for which no efficacious therapy is available. There is now clear evidence that SARS is caused by a previously unknown coronavirus, provisionally termed SARS coronavirus (SARS-CoV) (Peiris et al., 2003b;Drosten et al., 2003;Ksiazek et al., 2003;Fouchier et al., 2003). Genome sequences of SARS-CoV isolates obtained from a number of index patients have been published recently and provide important information on the organization, phylogeny and variability of the 29?7 kb positive-strand RNA genome of SARS-CoV (Rota et al., 2003;Marra et al., 2003;Ruan et al., 2003). By analogy with other coronaviruses (Lai & Holmes, 2001;Gorbalenya, 2001), SARS-CoV gene expression is expected to involve complex transcriptional, translational and post-translational regulatory mechanisms, whose molecular details remain to be determined. SARS-CoV genome expression starts with the translation of two large replicative polyproteins, pp1a (486 kDa) and pp1ab (790 kDa), which are encoded by the viral replicase gene (21 221 nt) that comprises ORFs 1a and 1b (Fig. 1). Expression of the ORF1b-encoded region of pp1ab is predicted to involve ribosomal frameshifting into the 21 frame just upstream of the ORF1a translation termination codon (Brierley et al., 1989). The pp1a and pp1ab polyproteins are processed by viral proteinases to yield the functional components of the membrane-bound replicase complex (Ziebuhr et al., 2000). In contrast to most other coronaviruses, which use three proteinase activities for replicase polyprotein processing (Ziebuhr et ...

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The Group-Specific Murine Coronavirus Genes Are Not Essential, but Their Deletion, by Reverse Genetics, Is Attenuating in the Natural Host

Cited by 218 publications

References 45 publications

Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus

Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus

Coronavirus avian infectious bronchitis virus

Mechanisms and enzymes involved in SARS coronavirus genome expression

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