Coronaviruses as Vectors: Stability of Foreign Gene Expression

Haan, Cornelis A. M. de; Haijema, Bert Jan; Boss, David S.; Heuts, Frank; Rottier, Peter J. M.

doi:10.1128/jvi.79.20.12742-12751.2005

Cited by 36 publications

(50 citation statements)

References 63 publications

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“…Still, little is known about how and when CoVs can incorporate novel genes into their genomes. The technical difficulties observed with the usage of CoV-based vectors for heterologous gene expression indicate that, at least in vitro, the introduction of foreign genes into a CoV genome is not an easy task (de Haan et al, 2005;Sola et al, 2003). Additionally, there are many examples of smaller RNA viruses containing numerous accessory genes that enhance virulence, such as HIV-1 at only a third of the typical CoV genome size (Malim and Emerman, 2008).…”

Section: Discussionmentioning

confidence: 99%

Ecology, evolution and classification of bat coronaviruses in the aftermath of SARS

2014

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In 2002/2003, a novel coronavirus (CoV) caused a pandemic, infecting more than 8000 people, of whom nearly 10% died. This virus, termed severe acute respiratory syndrome-CoV was linked to a zoonotic origin from rhinolophid bats in 2005. Since then, numerous studies have described novel bat CoVs, including close relatives of the newly emerging Middle East respiratory syndrome (MERS)-CoV. In this paper we discuss CoV genomic properties and compare different taxonomic approaches in light of the technical difficulties of obtaining full genomic sequences directly from bat specimens. We first present an overview of the available studies on bat CoVs, with details on their chiropteran hosts, then comparatively analyze the increase in bat CoV studies and novel genomic sequences obtained since the SARS pandemic. We then conduct a comprehensive phylogenetic analysis of the genera Alpha- and Betacoronavirus, to show that bats harbour more CoV diversity than other mammalian hosts and are widely represented in most, but not all parts of the tree of mammalian CoVs. We next discuss preliminary evidence for phylogenetic co-segregation of CoVs and bat hosts encompassing the Betacoronavirus clades b and d, with an emphasis on the sampling bias that exists among bat species and other mammals, then present examples of CoVs infecting different hosts on the one hand and viruses apparently confined to host genera on the other. We also demonstrate a geographic bias within available studies on bat CoVs, and identify a critical lack of information from biodiversity hotspots in Africa, Asia and Latin America. We then present evidence for a zoonotic origin of four of the six known human CoVs (HCoV), three of which likely involved bats, namely SARS-CoV, MERS-CoV and HCoV-229E; compare the available data on CoV pathogenesis in bats to that in other mammalian hosts; and discuss hypotheses on the putative insect origins of CoV ancestors. Finally, we suggest caution with conclusions on the zoonotic potential of bat viruses, based only on genomic sequence data, and emphasize the need to preserve these ecologically highly relevant animals. This paper forms part of a symposium in Antiviral Research on "from SARS to MERS: 10years of research on highly pathogenic human coronaviruses".

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Section: Discussionmentioning

confidence: 99%

Ecology, evolution and classification of bat coronaviruses in the aftermath of SARS

2014

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“…It is likely that foreign genes may contain sequences that make them more susceptible to mutation or recombination during coronavirus replication. For example, instability caused by the firefly luciferase in recombinant MHV might the associated with its high GC content (46.7%) when compared to the coronavirus genome (MHV, 41.8%; FIPV, 38.1%) (de Haan et al, 2005). Indeed, it was shown for poliovirus vectors that manipulation of the G/C contents increased the genetic stability of foreign inserts (Lee et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…These viruses, however, are inherently more prone to genetic instability, and this might particularly be the case for coronaviruses in view of the documented high frequency of recombination (Lai, 1996). Nevertheless, coronaviruses have been shown to accept and express foreign genes, making them attractive candidates for gene therapy vectors and vaccine development (Alonso et al, 2002;Curtis et al, 2002;de Haan et al, 2003de Haan et al, , 2005Enjuanes et al, 2001;Hackney et al, 2003;Ortego et al, 2002;Sola et al, 2003;Thiel et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…The first system, the so-called helperdependent expression systems, was employed to express several heterogonous genes, such as chloramphenicol acetyltransfererase (CAT) gene, ␤-glucuronidase (GUS) gene, green fluorescent protein (GFP) gene, firefly luciferase (LUC) gene and interferon-␥ (IFN-␥) gene by using coronavirus-derived minigenomes from mouse hepatitis virus (MHV), transmissible gastroenteritis virus (TGEV), human coronavirus 229E (HcoV-229E) and IBV (Alonso et al, 2002;Hackney et al, 2003;Izeta et al, 1997;Lin and Lai, 1993;Thiel et al, 2003;Zhang et al, 1997). The second type of expression systems based on reverse genetics of coronaviruses permits the expression of heterogonous genes by construction of recombinant viruses carrying foreign genes in the viral genome (de Haan et al, 2003(de Haan et al, , 2005Le et al, 2007;Youn et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Towards construction of viral vectors based on avian coronavirus infectious bronchitis virus for gene delivery and vaccine development

Shen

Fang

Chen

et al. 2009

Journal of Virological Methods

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a b s t r a c tManipulation of the coronavirus genome to accommodate and express foreign genes is an attractive approach for gene delivery and vaccine development. By using an infectious cloning system developed recently for the avian coronavirus infectious bronchitis virus (IBV), the enhanced green fluorescent protein (EGFP) gene, the firefly luciferase gene and several host and viral genes (eIF3f, SARS ORF6, Dengue virus 1 core protein gene) were inserted into various positions of the IBV genome, and the effects on gene expression, virus recovery, and stability in cell culture were studied. Selected viruses were also inoculated into chicken embryos for studies of foreign gene expression at different tissue level. The results demonstrated the stability of recombinant viruses depends on the intrinsic properties of the foreign gene itself as well as the position at which the foreign genes were inserted. For unstable viruses, the loss of expression of the inserted genes was found to result from a large deletion of the inserted gene and even IBV backbone sequences. This represents a promising system for development of coronavirus-based gene delivery vectors and vaccines against coronavirus and other viral infections in chicken.

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“…MHV-EFLM and FIPV-3abcFL are viruses containing a firefly luciferase gene, respectively, in a MHV A59 and FIPV 79-1146 background (de Haan et al, 2005). Growth properties and infectivity are similar to the parental viruses (de Haan et al, 2003).…”

Section: Cells Virusesmentioning

confidence: 99%

Antiviral activity of carbohydrate-binding agents against Nidovirales in cell culture

et al. 2007

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Coronaviruses are important human and animal pathogens, the relevance of which increased due to the emergence of new human coronaviruses like SARS-CoV, HKU1 and NL63. Together with toroviruses, arteriviruses, and roniviruses the coronaviruses belong to the order Nidovirales. So far antivirals are hardly available to combat infections with viruses of this order. Therefore, various antiviral strategies to counter nidoviral infections are under evaluation. Lectins, which bind to N-linked oligosaccharide elements of enveloped viruses, can be considered as a conceptionally new class of virus inhibitors. These agents were recently evaluated for their antiviral activity towards a variety of enveloped viruses and were shown in most cases to inhibit virus infection at low concentrations. However, limited knowledge is available for their efficacy towards nidoviruses. In this article the application of the plant lectins Hippeastrum hybrid agglutinin (HHA), Galanthus nivalis agglutinin (GNA), Cymbidium sp. agglutinin (CA) and Urtica dioica agglutinin (UDA) as well as non-plant derived pradimicin-A (PRM-A) and cyanovirin-N (CV-N) as potential antiviral agents was evaluated. Three antiviral tests were compared based on different evaluation principles: cell viability (MTT-based colorimetric assay), number of infected cells (immunoperoxidase assay) and amount of viral protein expression (luciferase-based assay). The presence of carbohydrate-binding agents strongly inhibited coronaviruses (transmissible gastroenteritis virus, infectious bronchitis virus, feline coronaviruses serotypes I and II, mouse hepatitis virus), arteriviruses (equine arteritis virus and porcine respiratory and reproductive syndrome virus) and torovirus (equine Berne virus). Remarkably, serotype II feline coronaviruses and arteriviruses were not inhibited by PRM-A, in contrast to the other viruses tested.

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Coronaviruses as Vectors: Stability of Foreign Gene Expression

Cited by 36 publications

References 63 publications

Ecology, evolution and classification of bat coronaviruses in the aftermath of SARS

Ecology, evolution and classification of bat coronaviruses in the aftermath of SARS

Towards construction of viral vectors based on avian coronavirus infectious bronchitis virus for gene delivery and vaccine development

Antiviral activity of carbohydrate-binding agents against Nidovirales in cell culture

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