A translation-attenuating intraleader open reading frame is selected on coronavirus mRNAs during persistent infection.

Hofmann, Martin; Senanayake, Savithra D.; Brian, David A.

doi:10.1073/pnas.90.24.11733

Cited by 43 publications

(58 citation statements)

References 41 publications

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“…It has been shown that the 5Ј UTRs of CoVs can influence the capacity of the virus to replicate in cells (46). Although the 5Ј UTR in the synthetic Bat-SCoV originated from SARS-CoV, the sole difference between Bat-SCoV, which was not capable of amplification in cell culture, and Bat-SRBD, which could be recovered, was the RBD derived from SARS-CoV.…”

Section: Discussionmentioning

confidence: 99%

Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice

Becker¹,

Graham²,

Donaldson³

et al. 2008

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

248

265

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Defining prospective pathways by which zoonoses evolve and emerge as human pathogens is critical for anticipating and controlling both natural and deliberate pandemics. However, predicting tenable pathways of animal-to-human movement has been hindered by challenges in identifying reservoir species, cultivating zoonotic organisms in culture, and isolating full-length genomes for cloning and genetic studies. The ability to design and recover pathogens reconstituted from synthesized cDNAs has the potential to overcome these obstacles by allowing studies of replication and pathogenesis without identification of reservoir species or cultivation of primary isolates. Here, we report the design, synthesis, and recovery of the largest synthetic replicating life form, a 29.7-kb bat severe acute respiratory syndrome (SARS)-like coronavirus (Bat-SCoV), a likely progenitor to the SARS-CoV epidemic. To test a possible route of emergence from the noncultivable Bat-SCoV to human SARS-CoV, we designed a consensus Bat-SCoV genome and replaced the Bat-SCoV Spike receptor-binding domain (RBD) with the SARS-CoV RBD (Bat-SRBD). Bat-SRBD was infectious in cell culture and in mice and was efficiently neutralized by antibodies specific for both bat and human CoV Spike proteins. Rational design, synthesis, and recovery of hypothetical recombinant viruses can be used to investigate mechanisms of transspecies movement of zoonoses and has great potential to aid in rapid public health responses to known or predicted emerging microbial threats.emerging pathogens ͉ synthetic biology ͉ vaccine development ͉ zoonoses

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Section: Discussionmentioning

confidence: 99%

Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice

Becker¹,

Graham²,

Donaldson³

et al. 2008

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

248

265

View full text Add to dashboard Cite

show abstract

“…In the 5h leader of a number of eukaryotic mRNAs such short ORFs regulate the rate of translation of a downstream reading frame (Kozak, 1991). Although the functionality of the various arterivirus intraleader ORFs remains to be proven, it is interesting to note that similar intraleader ORFs can arise during persistent coronavirus infections (Hofmann et al, 1993 ;Chen & Baric, 1995).…”

Section: Genome Properties and Organizationmentioning

confidence: 99%

The molecular biology of arteriviruses.

Snijder¹,

Meulenberg²

1998

Journal of General Virology

746

671

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“…Although mechanisms underlying these phenomena are not completely understood, it has been shown that, in some cases, virus persistence is associated with the selection of viruses containing mutations that downregulate and/or inactivate a critical virus gene(s) (Borzakian et al, 1992;Hofmann et al, 1993). The IBDV genome harbours three open reading frames (ORFs) encoding: (i) the RdRp; (ii) a large polyprotein containing three domains, corresponding to the capsid protein precursor (pVP2), the viral protease (VP4) and a multitasking structural polypeptide (VP3); and (iii) a 17 kDa polypeptide, VP5, that accumulates at the cell membrane (Lombardo et al, 2000).…”

mentioning

confidence: 99%

Infectious bursal disease virus persistently infects bursal B-lymphoid DT40 cells

Delgui

González

Rodrı́guez

2009

Journal of General Virology

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Infectious bursal disease virus (IBDV), an important avian pathogen, exhibits a specific tropism for immature B-lymphocyte populations. We have investigated the ability of IBDV to replicate in chicken B-lymphoid DT40 cells, a tumour cell line derived from the bursa of Fabricius of a chicken infected with avian leukosis virus. Our results show that IBDV persistently infects DT40 cells. Establishment of the persistent infection is associated with an extensive remodelling of the hypervariable region of the VP2 capsid polypeptide, accumulating 14 amino acid changes during the first 60 days of the persistent infection. The amino acid sequence of the non-structural VP5 polypeptide, involved in virus dissemination, is not altered during the persistent infection. Results described in this report constitute the first demonstration of the ability of IBDV to establish a persistent infection in vitro.Infectious bursal disease virus (IBDV), an avian pathogen responsible for a highly contagious immunosuppressive disease, is the best-characterized member of the family Birnaviridae. Birnaviruses are naked, icosahedral viruses with bipartite, double-stranded RNA genomes (Dobos et al., 1979). Although the last few years have witnessed major progress in the understanding of IBDV molecular and structural biology aspects, key issues concerning the virus replication programme remain poorly characterized. This lack of information is exemplified by the fact that, although the tropism of IBDV for bursal B-lymphocyte populations was first described and characterized extensively over 25 years ago (Becht, 1980;Kibenge et al., 1988), the discovery of the mechanism(s) governing this phenomenon still represents the holy grail of IBDV biology.Propagation of IBDV field isolates in tissue culture requires previous adaptation involving serial virus passage, a process that invariably leads to the introduction of mutations at specific residues on the VP2 capsid polypeptide, as well as a significant reduction of virus virulence (Cursiefen et al., 1979; Hassan et al., 1996;Lange et al., 1987; Yamaguchi et al., 1996a, b). This phenomenon constitutes a major obstacle to characterizing the interaction of pathogenic IBDV strains with susceptible host cells.In a recent report, Terasaki et al. (2008) showed that very virulent IBDV isolates can be grown directly in chicken lymphoid DT40 tumour cells infected persistently with avian leukosis virus (ALV) (Baba et al., 1985), without the requirement for a preliminary adaptation process. Most importantly, serial passage in this cell line does not result in the incorporation of mutations at the specific VP2 residues. Additionally, DT40 cells show an extremely high frequency of homologous recombination (Buerstedde & Takeda, 1991). This property has been exploited widely for the generation of derivative cell lines in which selected target genes are inactivated (Winding & Berchtold, 2001). Accordingly, DT40 cells appear to be an excellent candidate system to undertake a systematic analysis aimed at determining the ...

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A translation-attenuating intraleader open reading frame is selected on coronavirus mRNAs during persistent infection.

Cited by 43 publications

References 41 publications

Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice

Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice

The molecular biology of arteriviruses.

Infectious bursal disease virus persistently infects bursal B-lymphoid DT40 cells

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