A recombinant adenovirus bicistronically expressing porcine interferon-α and interferon-γ enhances antiviral effects against foot-and-mouth disease virus

Kim, Su-Mi; Kim, Se-Kyung; Park, Jong Hyeon; Lee, Kwang‐Nyeong; Ko, Young-Joon; Lee, Hyang-Sim; Seo, Min-Goo; Shin, Yeun-Kyung

doi:10.1016/j.antiviral.2014.01.014

Cited by 28 publications

(29 citation statements)

References 43 publications

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“…Ad-porcine IFN-␣␥ can suppress FMDV more effectively in animals through a synergistic effect involving IFN-␣, which directly suppresses FMDV, and IFN-␥, which plays an important role in T-cell-mediated immunity. The efficacy of Ad-porcine IFN-␣␥ in controlling FMDV replication has been proven indirectly as well, by inducing various IFN-stimulated genes (ISGs) (22). Ad-porcine IFN-␣␥ not only has a direct suppressive effect on FMDV but also exerts an indirect antiviral effect through the induction of an immune response.…”

Section: Discussionmentioning

confidence: 99%

“…A mixture of adenoviruses expressing porcine IFN-␣ and porcine IFN-␥ had synergistically enhanced anti-FMDV effects compared with the effect of an adenovirus expressing a single IFN (31). The Ad-porcine IFN-␣␥ component in the treatment combination is a recombinant adenovirus that simultaneously expresses type I and type II IFNs (22). Ad-porcine IFN-␣␥ can suppress FMDV more effectively in animals through a synergistic effect involving IFN-␣, which directly suppresses FMDV, and IFN-␥, which plays an important role in T-cell-mediated immunity.…”

Section: Discussionmentioning

confidence: 99%

“…We previously developed two recombinant adenoviruses, namely, Ad-porcine IFN-␣␥, which simultaneously expresses type I and type II interferons, and Ad-3siRNA, which simultaneously expresses 3 siRNAs, to maximize the efficacy of interferon and siRNA (21,22).…”

Section: Discussionmentioning

confidence: 99%

“…All infections using FMDV were conducted in a biosafety level 3 containment facility at the Animal and Plant Quarantine Agency (QIA). The preparation of recombinant adenoviruses expressing 3 different siRNA sequences targeting mRNA encoding the nonstructural proteins 2B and 3C (Ad-3siRNA) or porcine IFN-␣ and IFN-␥ proteins (Ad-porcine IFN-␣␥) has been described previously (21,22). Amplified adenoviruses were purified using a ViraBind adenovirus purification kit (Cell Biolabs, San Diego, CA, USA) or a Vivapure AdenoPack 500 kit (Sartorius, Goettingen, Germany).…”

Section: Cells Viruses and Virus Titrationsmentioning

confidence: 99%

“…Viruses can eventually develop resistance mechanisms through point mutations to evade targeted small interfering RNAs (siRNAs), although siRNAs can offer rapid antiviral treatment (19,20). We have developed recombinant adenoviruses that simultaneously express porcine alpha interferon (IFN-␣) and IFN-␥ (referred to here as Ad-porcine IFN-␣␥) and multiple (n ϭ 3) siRNAs targeting nonstructural proteins of FMDV (referred to here as Ad-3siRNA) to enhance the inhibitory effects of these antiviral agents observed in previous studies (21,22). Importantly, both classes of antiviral agents operate through distinct mechanisms and are effective against a broad range of FMDV serotypes.…”

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confidence: 99%

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Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

Kim

Park

Lee

et al. 2015

J Virol

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Because the currently available vaccines against foot-and-mouth disease (FMD) provide no protection until 4 to 7 days postvaccination, the only alternative method to halt the spread of the FMD virus (FMDV) during outbreaks is the application of antiviral agents. Combination treatment strategies have been used to enhance the efficacy of antiviral agents, and such strategies may be advantageous in overcoming viral mechanisms of resistance to antiviral treatments. We have developed recombinant adenoviruses (Ads) for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-␣␥) as well as 3 small interfering RNAs (Ad-3siRNA) targeting FMDV mRNAs encoding nonstructural proteins. The antiviral effects of Ad-porcine IFN-␣␥ and Ad-3siRNA expression were tested in combination in porcine cells, suckling mice, and swine. We observed enhanced antiviral effects in porcine cells and mice as well as robust protection against the highly pathogenic strain O/Andong/ SKR/2010 and increased expression of cytokines in swine following combination treatment. In addition, we showed that combination treatment was effective against all serotypes of FMDV. Therefore, we suggest that the combined treatment with Adporcine IFN-␣␥ and Ad-3siRNA may offer fast-acting antiviral protection and be used with a vaccine during the period that the vaccine does not provide protection against FMD. IMPORTANCEThe use of current foot-and-mouth disease (FMD) vaccines to induce rapid protection provides limited effectiveness because the protection does not become effective until a minimum of 4 days after vaccination. Therefore, during outbreaks antiviral agents remain the only available treatment to confer rapid protection and reduce the spread of foot-and-mouth disease virus (FMDV) in livestock until vaccine-induced protective immunity can become effective. Interferons (IFNs) and small interfering RNAs (siRNAs) have been reported to be effective antiviral agents against FMDV, although the virus has associated mechanisms of resistance to type I interferons and siRNAs. We have developed recombinant adenoviruses for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-␣␥) as well as 3 small interfering RNAs (Ad-3siRNA) to enhance the inhibitory effects of these antiviral agents observed in previous studies. Here, we show enhanced antiviral effects against FMDV by combination treatment with Ad-porcine IFN-␣␥ and Ad-3siRNA to overcome the mechanisms of resistance of FMDV in swine.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cells Viruses and Virus Titrationsmentioning

confidence: 99%

mentioning

confidence: 99%

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Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

Kim

Park

Lee

et al. 2015

J Virol

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Antiviral activity of porcine interferon omega 7 against foot‐and‐mouth disease virus in vitro

Zhao

Gong

et al. 2018

Journal of Medical Virology

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Foot-and-mouth disease (FMD) is a disease of worldwide economic importance, and vaccines play an important role in preventing FMDV outbreaks. However, new control strategies are still needed since FMDV outbreaks still occur in some disease-free countries. Currently, interferon (IFN)-based strategies have been demonstrated to be an efficient biotherapeutic option against FMDV; however, interferon omega (IFN-ω) has not yet been assessed in this capacity. Thus, this study evaluated the antiviral activity of porcine IFN omega 7 (PoIFN-ω7) against FMDV. After the PoIFN-ω7 was expressed and purified, cell proliferation assays and quantitative real-time reverse transciption-polymerase chain reaction were used to evaluate the effective anti-cytopathic concentration of PoIFN-ω7 and its effectiveness pre- and post-infection with FMDV in swine kidney cells (IBRS-2). Results showed the rHis-PoIFN-ω7 fusion protein was considerably expressed using Escherichia coli BL21 (DE3) strain, and the recombinant protein exhibited significant in vitro protection against FMDV, including two strains belonging to type O and A FMDV, respectively. In addition, PoIFN-ω7 upregulated the transcription of Mx1, ISG15, OAS1, and PKR genes. These findings indicated that IFN-ω has the potential for serving as a useful therapeutic agent to prevent FMDV or other viral outbreaks in pigs.

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Expression of porcine interferon-α and its bioactivity analysis in vitro and in vivo

Wang

Liang

et al. 2020

Bioprocess Biosyst Eng

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A recombinant adenovirus bicistronically expressing porcine interferon-α and interferon-γ enhances antiviral effects against foot-and-mouth disease virus

Cited by 28 publications

References 43 publications

Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

Antiviral activity of porcine interferon omega 7 against foot‐and‐mouth disease virus in vitro

Expression of porcine interferon-α and its bioactivity analysis in vitro and in vivo

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