Virus-based vectors for gene expression in mammalian cells: Coronavirus

Enjuanes, Luis; Almazán, Fernando; Ortego, Javier

doi:10.1016/s0167-7306(03)38010-x

Cited by 8 publications

(8 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the retrovirus vectors and lentivirus vectors already established as a practical tool for gene transfer, RNA virus vectors based on alphaviruses, rhabdoviruses, coronaviruses, picornaviruses, and paramyxoviruses have been developed (43,44). However, except for the vectors belonging to Retroviridae that stabilize their genome cDNA by chromosomal insertion, most RNA virus vectors have not been considered as tools for stable and persistent gene expression because of their potent cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Persistent and Stable Gene Expression by a Cytoplasmic RNA Replicon Based on a Noncytopathic Variant Sendai Virus

Nishimura

Segawa

Goto

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Persistent and stable expression of foreign genes has been achieved in mammalian cells by integrating the genes into the host chromosomes. However, this approach has several shortcomings in practical applications. For example, large scale production of protein pharmaceutics frequently requires laborious amplification of the inserted genes to optimize the gene expression. The random chromosomal insertion of exogenous DNA also results occasionally in malignant transformation of normal tissue cells, raising safety concerns in medical applications. Here we report a novel cytoplasmic RNA replicon capable of expressing installed genes stably without chromosome insertion. This system is based on the RNA genome of a noncytopathic variant Sendai virus strain, Cl.151. We found that this variant virus establishes stable symbiosis with host cells by escaping from retinoic acid-inducible gene I-interferon regulatory factor 3-mediated antiviral machinery. Using a cloned genome cDNA of Sendai virus Cl.151, we developed a recombinant RNA installed with exogenous marker genes that was maintained stably in the cytoplasm as a high copy replicon (about 4 ؋ 10 4 copies/cell) without interfering with normal cellular function. Strong expression of the marker genes persisted for more than 6 months in various types of cultured cells and for at least two months in rat colonic mucosa without any apparent side effects. This stable RNA replicon is a potentially valuable genetic platform for various biological applications.

show abstract

Section: Discussionmentioning

confidence: 99%

Persistent and Stable Gene Expression by a Cytoplasmic RNA Replicon Based on a Noncytopathic Variant Sendai Virus

Nishimura

Segawa

Goto

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Because coronavirus tissue specificity and species specificity can be engineered, the same expression systems can be used to target expression to different organs and animals species, including humans (22). The humanized mice described here will allow studies of virus and viral vector tropism, replication, recombination, and spread in an immunocompromised situation.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, several infectious cDNA clones of porcine, murine, and human coronaviruses have been isolated (18)(19)(20)(21), facilitating reverse genetics of coronavirus to study the mechanism of replication and the development of vectors for vaccine development and gene therapy (22). Although testing of coronavirus vector efficacy in domestic and laboratory animal models is amenable, animal models to test coronavirus-derived human vectors have only been described for SARS coronavirus (23,24) and HCoV-OC43 (25,26).…”

mentioning

confidence: 99%

Development of a transgenic mouse model susceptible to human coronavirus 229E

Lassnig

Sánchez

Egerbacher

et al. 2005

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

Self Cite

View full text Add to dashboard Cite

Human coronavirus (HCoV) 229E is a group 1 coronavirus and is specific to humans. So far, no animal model is available to study the pathogenesis of infection by HCoV-229E. We show here that the expression of aminopeptidase N (APN, also termed CD13), the receptor for HCoV-229E, is required but not sufficient to confer susceptibility in vivo. HCoV-229E infection was facilitated by crossing APN transgenic mice into signal transducers and activators of transcription (Stat) 1 null mice and by adaptation of HCoV-229E to grow in primary APN transgenic, Stat1 null fibroblasts. Double transgenic mice allow the study of human coronavirus group 1 infections in an animal model, in particular, viral tropism, replication, recombination, and spread in an immunocompromised situation. Furthermore, these mice provide an important tool for the evaluation of biosafety and efficacy of coronavirus-based vectors.

show abstract

“…Further, it was recently reported that MHV ns2 protein acts as a 2=-5=-phosphodiesterase that reduces the amount of 2=-5=-oligoadenylates, avoiding the activation of RNase L and, as a consequence, reducing RNA degradation during viral infection and type I IFN production (24). Transmissible gastroenteritis virus (TGEV) is an Alphacoronavirus that contains three accessory genes: 3a, 3b, and 7 (44)(45)(46). TGEV gene 7 is located at the 3= end of the genome and is the last ORF.…”

mentioning

confidence: 99%

Alphacoronavirus Protein 7 Modulates Host Innate Immune Response

Cruz

Becares

Sola

et al. 2013

J Virol

Self Cite

View full text Add to dashboard Cite

bInnate immune response is the first line of antiviral defense resulting, in most cases, in pathogen clearance with minimal clinical consequences. Viruses have developed diverse strategies to subvert host defense mechanisms and increase their survival. In the transmissible gastroenteritis virus (TGEV) as a model, we previously reported that accessory gene 7 counteracts the host antiviral response by associating with the catalytic subunit of protein phosphatase 1 (PP1c). In the present work, the effect of the absence of gene 7 on the host cell, during infection, was further analyzed by transcriptomic analysis. The pattern of gene expression of cells infected with a recombinant mutant TGEV, lacking gene 7 expression (rTGEV-⌬7), was compared to that of cells infected with the parental virus (rTGEV-wt). Genes involved in the immune response, the interferon response, and inflammation were upregulated during TGEV infection in the absence of gene 7. An exacerbated innate immune response during infection with rTGEV-⌬7 virus was observed both in vitro and in vivo. An increase in macrophage recruitment and activation in lung tissues infected with rTGEV-⌬7 virus was observed compared to cells infected with the parental virus. In summary, the absence of protein 7 both in vitro and in vivo led to increased proinflammatory responses and acute tissue damage after infection. In a porcine animal model, which is immunologically similar to humans, we present a novel example of how viral proteins counteract host antiviral pathways to determine the infection outcome and pathogenesis.

show abstract

Virus-based vectors for gene expression in mammalian cells: Coronavirus

Cited by 8 publications

References 63 publications

Persistent and Stable Gene Expression by a Cytoplasmic RNA Replicon Based on a Noncytopathic Variant Sendai Virus

Persistent and Stable Gene Expression by a Cytoplasmic RNA Replicon Based on a Noncytopathic Variant Sendai Virus

Development of a transgenic mouse model susceptible to human coronavirus 229E

Alphacoronavirus Protein 7 Modulates Host Innate Immune Response

Contact Info

Product

Resources

About