Review

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Open AccessReview

Public Acceptance of Plant Biotechnology and GM Crops

by Jan M. Lucht

Viruses 2015, 7(8), 4254-4281; https://doi.org/10.3390/v7082819 - 30 Jul 2015

Cited by 268 | Viewed by 37200

A wide gap exists between the rapid acceptance of genetically modified (GM) crops for cultivation by farmers in many countries and in the global markets for food and feed, and the often-limited acceptance by consumers. This review contrasts the advances of practical applications [...] Read more.

A wide gap exists between the rapid acceptance of genetically modified (GM) crops for cultivation by farmers in many countries and in the global markets for food and feed, and the often-limited acceptance by consumers. This review contrasts the advances of practical applications of agricultural biotechnology with the divergent paths—also affecting the development of virus resistant transgenic crops—of political and regulatory frameworks for GM crops and food in different parts of the world. These have also shaped the different opinions of consumers. Important factors influencing consumer’s attitudes are the perception of risks and benefits, knowledge and trust, and personal values. Recent political and societal developments show a hardening of the negative environment for agricultural biotechnology in Europe, a growing discussion—including calls for labeling of GM food—in the USA, and a careful development in China towards a possible authorization of GM rice that takes the societal discussions into account. New breeding techniques address some consumers’ concerns with transgenic crops, but it is not clear yet how consumers’ attitudes towards them will develop. Discussions about agriculture would be more productive, if they would focus less on technologies, but on common aims and underlying values. Full article

(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)

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Open AccessReview

CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape

by Gero Hütter, Josef Bodor, Scott Ledger, Maureen Boyd, Michelle Millington, Marlene Tsie and Geoff Symonds

Viruses 2015, 7(8), 4186-4203; https://doi.org/10.3390/v7082816 - 27 Jul 2015

Cited by 81 | Viewed by 12557

Abstract

Allogeneic transplantation with CCR5-delta 32 (CCR5-d32) homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a [...] Read more.

Allogeneic transplantation with CCR5-delta 32 (CCR5-d32) homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC) to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN), clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9), transcription activator-like effectors nuclease (TALEN), short hairpin RNA (shRNA), and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape. Full article

(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)

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Open AccessReview

Bone Marrow Gene Therapy for HIV/AIDS

by Elena Herrera-Carrillo and Ben Berkhout

Viruses 2015, 7(7), 3910-3936; https://doi.org/10.3390/v7072804 - 17 Jul 2015

Cited by 19 | Viewed by 15449

Abstract

Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV). This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs) with long-term expression of therapeutic transgenes [...] Read more.

Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV). This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs) with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described. Full article

(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)

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Open AccessReview

Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems

by Marta Trevisan, Alessandro Sinigaglia, Giovanna Desole, Alessandro Berto, Monia Pacenti, Giorgio Palù and Luisa Barzon

Viruses 2015, 7(7), 3835-3856; https://doi.org/10.3390/v7072800 - 13 Jul 2015

Cited by 23 | Viewed by 7526

Abstract

The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs), which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of [...] Read more.

The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs), which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host–pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance. Full article

(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)

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Open AccessReview

Cloned Defective Interfering Influenza RNA and a Possible Pan-Specific Treatment of Respiratory Virus Diseases

by Nigel J. Dimmock and Andrew J. Easton

Viruses 2015, 7(7), 3768-3788; https://doi.org/10.3390/v7072796 - 08 Jul 2015

Cited by 49 | Viewed by 7225

Abstract

Defective interfering (DI) genomes are characterised by their ability to interfere with the replication of the virus from which they were derived, and other genetically compatible viruses. DI genomes are synthesized by nearly all known viruses and represent a vast natural reservoir of [...] Read more.

Defective interfering (DI) genomes are characterised by their ability to interfere with the replication of the virus from which they were derived, and other genetically compatible viruses. DI genomes are synthesized by nearly all known viruses and represent a vast natural reservoir of antivirals that can potentially be exploited for use in the clinic. This review describes the application of DI virus to protect from virus-associated diseases in vivo using as an example a highly active cloned influenza A DI genome and virus that protects broadly in preclinical trials against different subtypes of influenza A and against non-influenza A respiratory viruses. This influenza A-derived DI genome protects by two totally different mechanisms: molecular interference with influenza A replication and by stimulating innate immunity that acts against non-influenza A viruses. The review considers what is needed to develop DI genomes to the point of entry into clinical trials. Full article

(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)

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Open AccessReview

Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence

by Thibault Mesplède and Mark A. Wainberg

Viruses 2015, 7(7), 3703-3718; https://doi.org/10.3390/v7072790 - 07 Jul 2015

Cited by 45 | Viewed by 7304

Abstract

Drug resistance prevents the successful treatment of HIV-positive individuals by decreasing viral sensitivity to a drug or a class of drugs. In addition to transmitted resistant viruses, treatment-naïve individuals can be confronted with the problem of drug resistance through de novo emergence of [...] Read more.

Drug resistance prevents the successful treatment of HIV-positive individuals by decreasing viral sensitivity to a drug or a class of drugs. In addition to transmitted resistant viruses, treatment-naïve individuals can be confronted with the problem of drug resistance through de novo emergence of such variants. Resistant viruses have been reported for every antiretroviral drug tested so far, including the integrase strand transfer inhibitors raltegravir, elvitegravir and dolutegravir. However, de novo resistant variants against dolutegravir have been found in treatment-experienced but not in treatment-naïve individuals, a characteristic that is unique amongst antiretroviral drugs. We review here the issue of drug resistance against integrase strand transfer inhibitors as well as both pre-clinical and clinical studies that have led to the identification of the R263K mutation in integrase as a signature resistance substitution for dolutegravir. We also discuss how the topic of drug resistance against integrase strand transfer inhibitors may have relevance in regard to the nature of the HIV reservoir and possible HIV curative strategies. Full article

(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)

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Open AccessReview

Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses

by Danielle Blondel, Ghizlane Maarifi, Sébastien Nisole and Mounira K. Chelbi-Alix

Viruses 2015, 7(7), 3675-3702; https://doi.org/10.3390/v7072794 - 07 Jul 2015

Cited by 24 | Viewed by 11241

Abstract

Interferon (IFN) treatment induces the expression of hundreds of IFN-stimulated genes (ISGs). However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play [...] Read more.

Interferon (IFN) treatment induces the expression of hundreds of IFN-stimulated genes (ISGs). However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus replication at different stages via the induction of a variety of ISGs. This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell. Furthermore, this review will highlight how these viruses counteract the host IFN system. Full article

(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)

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Open AccessReview

Plant Translation Factors and Virus Resistance

by Hélène Sanfaçon

Viruses 2015, 7(7), 3392-3419; https://doi.org/10.3390/v7072778 - 24 Jun 2015

Cited by 187 | Viewed by 14954

Abstract

Plant viruses recruit cellular translation factors not only to translate their viral RNAs but also to regulate their replication and potentiate their local and systemic movement. Because of the virus dependence on cellular translation factors, it is perhaps not surprising that many natural [...] Read more.

Plant viruses recruit cellular translation factors not only to translate their viral RNAs but also to regulate their replication and potentiate their local and systemic movement. Because of the virus dependence on cellular translation factors, it is perhaps not surprising that many natural plant recessive resistance genes have been mapped to mutations of translation initiation factors eIF4E and eIF4G or their isoforms, eIFiso4E and eIFiso4G. The partial functional redundancy of these isoforms allows specific mutation or knock-down of one isoform to provide virus resistance without hindering the general health of the plant. New possible targets for antiviral strategies have also been identified following the characterization of other plant translation factors (eIF4A-like helicases, eIF3, eEF1A and eEF1B) that specifically interact with viral RNAs and proteins and regulate various aspects of the infection cycle. Emerging evidence that translation repression operates as an alternative antiviral RNA silencing mechanism is also discussed. Understanding the mechanisms that control the development of natural viral resistance and the emergence of virulent isolates in response to these plant defense responses will provide the basis for the selection of new sources of resistance and for the intelligent design of engineered resistance that is broad-spectrum and durable. Full article

(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)

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Open AccessReview

RNA Viruses and RNAi: Quasispecies Implications for Viral Escape

by John B. Presloid and Isabel S. Novella

Viruses 2015, 7(6), 3226-3240; https://doi.org/10.3390/v7062768 - 19 Jun 2015

Cited by 26 | Viewed by 6336

Abstract

Due to high mutation rates, populations of RNA viruses exist as a collection of closely related mutants known as a quasispecies. A consequence of error-prone replication is the potential for rapid adaptation of RNA viruses when a selective pressure is applied, including host [...] Read more.

Due to high mutation rates, populations of RNA viruses exist as a collection of closely related mutants known as a quasispecies. A consequence of error-prone replication is the potential for rapid adaptation of RNA viruses when a selective pressure is applied, including host immune systems and antiviral drugs. RNA interference (RNAi) acts to inhibit protein synthesis by targeting specific mRNAs for degradation and this process has been developed to target RNA viruses, exhibiting their potential as a therapeutic against infections. However, viruses containing mutations conferring resistance to RNAi were isolated in nearly all cases, underlining the problems of rapid viral evolution. Thus, while promising, the use of RNAi in treating or preventing viral diseases remains fraught with the typical complications that result from high specificity of the target, as seen in other antiviral regimens. Full article

(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)

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Open AccessReview

Important Role of the IL-32 Inflammatory Network in the Host Response against Viral Infection

by Yaqin Zhou and Ying Zhu

Viruses 2015, 7(6), 3116-3129; https://doi.org/10.3390/v7062762 - 16 Jun 2015

Cited by 23 | Viewed by 7546

Abstract

The pro-inflammatory cytokine interleukin (IL)-32 has gained much attention recently because of its important role in the inflammatory network. Since the discovery of IL-32 in 2005, our appreciation for its diverse roles continues to grow. Recent studies have discovered the antiviral effects induced [...] Read more.

The pro-inflammatory cytokine interleukin (IL)-32 has gained much attention recently because of its important role in the inflammatory network. Since the discovery of IL-32 in 2005, our appreciation for its diverse roles continues to grow. Recent studies have discovered the antiviral effects induced by IL-32 and its associated regulatory mechanisms. The interactions between IL-32 and various cytokines including cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), interferon (IFN)-λ1, interleukin (IL)-6, and soluble IL-6 receptor have been described. This review aims to integrate these new findings into explicit concepts and raises the intriguing possibility of IL-32 as a therapeutic target. Full article

(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)

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Open AccessReview

Engineering Viroid Resistance

by Athanasios Dalakouras, Elena Dadami and Michael Wassenegger

Viruses 2015, 7(2), 634-646; https://doi.org/10.3390/v7020634 - 10 Feb 2015

Cited by 21 | Viewed by 6770

Abstract

Viroids are non-encapsidated, non-coding, circular, single-stranded RNAs (ssRNAs). They are classified into the families Pospiviroidae and Avsunviroidae, whose members replicate in the nucleus and chloroplast of plant cells, respectively. Viroids have a wide host range, including crop and ornamental plants, and can [...] Read more.

Viroids are non-encapsidated, non-coding, circular, single-stranded RNAs (ssRNAs). They are classified into the families Pospiviroidae and Avsunviroidae, whose members replicate in the nucleus and chloroplast of plant cells, respectively. Viroids have a wide host range, including crop and ornamental plants, and can cause devastating diseases with significant economic losses. Thus, several viroids are world-wide, classified as quarantine pathogens and, hence, there is an urgent need for the development of robust antiviroid strategies. RNA silencing-based technologies seem to be a promising tool in this direction. Here, we review the recent advances concerning the complex interaction of viroids with the host’s RNA silencing machinery, evaluate past and present antiviroid approaches, and finally suggest alternative strategies that could potentially be employed in the future in order to achieve transgenic and non-transgenic viroid-free plants. Full article

(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)

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