Synthetic Viruses: An Inevitable Reality
Were meant as new strategies for fighting upcoming diseases.
Before the COVID-19 pandemic, we laypersons rarely read and heard about synthetic viruses. Volker Thiel argued that the advantages of synthetic viruses are major as they are an important mechanistic insight into critical determinants of virus tropism, transmission, and pathogenicity. Reflect upon the SARS virus, synthetic viruses may determine zoonotic infection: to understand cross-species transmission of contemporary virus strains and to assess the risk of emerging pandemic viruses. Wimmer and colleagues added that genome synthesis of both DNA and RNA viruses will lead to unprecedented possibilities in modifying naturally occurring genomes, thereby allowing new studies of viral genome architecture, viral gene expression, and gene function. The team is aware of the consequences of synthetic viruses as they mentioned the 'Dual use' concerns and total synthesis of viruses.
Reviving Old Virus
One of the stories about reviving viruses by applying synthetic biology was done by Tumpey and the team, thanks to Taubenberger et al.. By using the complete 1918 influenza virus coding sequence, they revived the Spanish flu virus which had lowered the average life expectancy in the United States by more than 10 years. The team in Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus explained reverse genetics to generate an influenza virus bearing all eight gene segments of the pandemic virus to study the properties associated with its extraordinary virulence. In reverse genetics, mutations are introduced into the DNA sequence of the target gene. The organism is then studied for phenotypic changes, and the genotype and phenotype can be precisely correlated. Rarely have we read in any research paper that the particular research was done by staff taking antiviral prophylaxis and using stringent biosafety precautions to protect the researchers, the environment, and the public. It proved to be as fatal as the original. When tested on mice, it killed the animals more quickly than any other flu virus ever tested.
Palese, Tumpey, and Garcia-Sastre in further reasonings resumed that this virus turned out to be highly virulent in the mouse model, more so than any other human influenza virus strain tested. It was also highly pathogenic for chicken embryos, capable of killing these embryos at very low doses. It was also able to grow in human tissue culture cells to high titers, and it replicated in cells in the absence of trypsin, which may also indicate high virulence. The trio concluded that the availability of the 1918 virus would contribute to understanding the mechanisms by which pandemic influenza viruses are transmitted from human to human and from one species to another. In the hope that the 2005 findings will provide better prevention and treatment strategies for the future, the authors believed that those would expand the knowledge of the biological and molecular properties of pandemic influenza viruses.
Infectious Virions Rescue
Gan et al., 2021 reported a developed new reverse genetics system for Ebola virus (EBOV) by only requiring transfection of a single element (viral RNA genome) into a helper cell line that had been engineered and optimized for its superior ability to support EBOV replication and propagation. A reverse genetics system is an important tool for studying viruses by producing mutant viruses or generating safer and more convenient model systems. The team reported the authentic response of the subviral system to antivirals and uncovered that the VP35 amount is critical for optimal virus replication. They also showed that fully infectious virions can be efficiently rescued by delivering the full-length EBOV genome into the same supporting cell, and the efficiency is not affected by genome polarity or virus variant specificity.
Detecting Host-Virus Chimeric and Enriching Viral Sequences
Recent studies have reported the presence of host-virus chimeric (HVC) RNA in data from SARS-CoV-2-infected cells and interpreted these findings as evidence of viral integration in the human genome as a potential pathogenic mechanism. This suggestion has fueled concerns about the long-term effects of current mRNA vaccines that incorporate elements of the viral genome. According to Yan et al. such events were rare. They developed a novel experimental approach to enrich SARS-CoV-2 sequences from bulk RNA of infected cells. This method enriched viral sequences but did not enrich HVC events, suggesting that the majority of HVC events are artifacts of library construction. They concluded that HVC events observed in RNA-sequencing libraries from SARS-CoV-2-infected cells are extremely rare and are likely artifacts arising from random template switching of reverse transcriptase and/or sequence alignment errors.
To Produce Vaccine Candidate Strains
In 2014 Yuko Uchida, Nobuhiro Takemae, and Takehiko Saito published the use of reverse genetics as an option to promptly produce an inactivated vaccine with better matching of antigenicity to a circulating strain. Reverse genetics for rotavirus vaccine developments were explained and summarized by Tirth Uprety, Dan Wang, and Feng Li in 2021.
Many pathogens were reported before but yet we had never thought thoroughly about which one was synthetic and which one wasn’t. Synthetic biology (viruses) was applied behind closed laboratory doors and introduced to humans through vaccines and therapeutic medicines. The uncertainty of viruses’ genome integration was understood comprehensively, yet quantitatively it was undecided. With governmental policies and health organizations' pieces of advice, we as laypersons are trapped in layers of confusion, especially by the media. Though the advantages of synthetic viruses were reported scientifically, we are vulnerable to being manipulated as many of those publications were funded by organizations with conflicts of interest. Trusting science is about relying on the conscience of those parties; seeing us as markets or patients.