RESUMEN
Biology can be misused, and the risk of this causing widespread harm increases in step with the rapid march of technological progress. A key security challenge involves attribution: determining, in the wake of a human-caused biological event, who was responsible. Recent scientific developments have demonstrated a capability for detecting whether an organism involved in such an event has been genetically modified and, if modified, to infer from its genetic sequence its likely lab of origin. We believe this technique could be developed into powerful forensic tools to aid the attribution of outbreaks caused by genetically engineered pathogens, and thus protect against the potential misuse of synthetic biology.
Asunto(s)
Bioterrorismo/prevención & control , ADN/análisis , Genética Forense/métodos , Organismos Modificados Genéticamente/genética , Medidas de Seguridad , Animales , Biotecnología , Control de Enfermedades Transmisibles/métodos , Enfermedades Transmisibles/microbiología , Enfermedades Transmisibles/transmisión , Conjuntos de Datos como Asunto , Ingeniería Genética , Humanos , Organismos Modificados Genéticamente/patogenicidad , Virulencia/genéticaRESUMEN
SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2, which emerged in China at the end of 2019, is responsible for a global health crisis resulting in the confinement of more than 3 billion people worldwide and the sharp decline of the world economy. In this context, a race against the clock is launched in order to develop a treatment to stop the pandemic as soon as possible. A study published in Nature by the Volker Thiel team reports the development of reverse genetics for SARS-CoV-2 allowing them to recreate the virus in just a few weeks. The perspectives of this work are very interesting since it will allow the genetic manipulation of the virus and thus the development of precious tools which will be useful to fight the infection. Even though this approach represents a technological leap that will improve our knowledge of the virus, it also carries the germ of possible misuse and the creation of the virus for malicious purposes. The advantages and disadvantages of recreating SARS-CoV-2 in this pandemic period are discussed in this mini-synthesis.
TITLE: Une course contre la montre - Création du SARS-CoV-2 en laboratoire, un mois après son émergence ! ABSTRACT: Le SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2), qui a émergé à la fin de l'année 2019 en République populaire de Chine, est responsable d'une crise sanitaire mondiale qui a entraîné le confinement de plus de 3 milliards d'individus et l'arrêt brutal de l'économie planétaire. Dans ce contexte, une course contre la montre est lancée afin de développer, dans les plus brefs délais, un traitement permettant d'enrayer la pandémie. Une étude de l'équipe de Volker Thiel, parue dans le journal Nature, rapporte la mise au point d'une technique de génétique inverse pour le SARS-CoV-2, leur ayant permis de recréer le virus en seulement quelques semaines. Les perspectives de ces travaux sont très intéressantes puisqu'elles permettent d'envisager la manipulation génétique du virus et ainsi le développement d'outils précieux qui seront utiles pour combattre l'infection. Si la technique représente également un saut technologique qui permettra d'améliorer nos connaissances sur le virus, elle porte aussi en elle le germe d'un possible mésusage et la création d'un virus à des fins malveillantes. Les avantages et inconvénients de recréer le SARS-CoV-2 dans cette période de pandémie sont discutés dans cet article.
Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/virología , Organismos Modificados Genéticamente , Pandemias , Neumonía Viral/virología , Genética Inversa/métodos , Betacoronavirus/patogenicidad , Derrame de Material Biológico , COVID-19 , Vacunas contra la COVID-19 , Cromosomas Artificiales de Levadura , Clonación Molecular/métodos , Coronaviridae/clasificación , Coronaviridae/genética , Coronaviridae/patogenicidad , Infecciones por Coronavirus/prevención & control , ADN Complementario/genética , Especificidad del Huésped , Humanos , Organismos Modificados Genéticamente/genética , Organismos Modificados Genéticamente/patogenicidad , Pandemias/prevención & control , Neumonía Viral/prevención & control , ARN Viral/genética , Recombinación Genética , Riesgo , SARS-CoV-2 , Vacunas ViralesRESUMEN
The ongoing pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the urgency to develop experimental systems for studying this virus and identifying countermeasures. We report a reverse genetic system for SARS-CoV-2. Seven complimentary DNA (cDNA) fragments spanning the SARS-CoV-2 genome were assembled into a full-genome cDNA. RNA transcribed from the full-genome cDNA was highly infectious after electroporation into cells, producing 2.9 × 106 plaque-forming unit (PFU)/mL of virus. Compared with a clinical isolate, the infectious-clone-derived SARS-CoV-2 (icSARS-CoV-2) exhibited similar plaque morphology, viral RNA profile, and replication kinetics. Additionally, icSARS-CoV-2 retained engineered molecular markers and did not acquire other mutations. We generated a stable mNeonGreen SARS-CoV-2 (icSARS-CoV-2-mNG) by introducing this reporter gene into ORF7 of the viral genome. icSARS-CoV-2-mNG was successfully used to evaluate the antiviral activities of interferon (IFN). Collectively, the reverse genetic system and reporter virus provide key reagents to study SARS-CoV-2 and develop countermeasures.
Asunto(s)
Betacoronavirus/genética , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/virología , ADN Complementario/genética , Organismos Modificados Genéticamente/genética , Organismos Modificados Genéticamente/patogenicidad , Neumonía Viral/virología , Animales , Antivirales/uso terapéutico , COVID-19 , Chlorocebus aethiops , Células Clonales , Infecciones por Coronavirus/tratamiento farmacológico , Genes Reporteros/genética , Genoma Viral/genética , Interferones/uso terapéutico , Pandemias , Neumonía Viral/tratamiento farmacológico , ARN Viral/genética , SARS-CoV-2 , Células Vero/virología , Replicación Viral/fisiologíaRESUMEN
Traditional restriction endonuclease-based cloning has been routinely used to generate replication-competent simian-human immunodeficiency viruses (SHIV) and simian tropic HIV (stHIV). This approach requires the existence of suitable restriction sites or the introduction of nucleotide changes to create them. Here, using an In-Fusion cloning technique that involves homologous recombination, we generated SHIVs and stHIVs based on epidemiologically linked clade C transmitted/founder HIV molecular clones from Zambia. Replacing vif from these HIV molecular clones with vif of SIVmac239 resulted in chimeric genomes used to generate infectious stHIV viruses. Likewise, exchanging HIV env genes and introducing N375 mutations to enhance macaque CD4 binding site and cloned into a SHIVAD8-EO backbone. The generated SHIVs and stHIV were infectious in TZMbl and ZB5 cells, as well as macaque PBMCs. Therefore, this method can replace traditional methods and be a valuable tool for the rapid generation and testing of molecular clones of stHIV and SHIV based on primary clinical isolates will be valuable to generate rapid novel challenge viruses for HIV vaccine/cure studies.
