Engineered Viral Resistance
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By Jamila Ahmed on Jul 27, 2020
Can humans become engineered to have viral resistance?
The viral protein genome-linked (VPg) binds directly to the host eukaryotic translation initiation factor 4E (eIF4E); this produces more viral proteins that are essential for viral replication and the subsequent viral infection. Some Arabidopsis thaliana mutants are naturally resistant to the tobacco etch virus. Mutations in the eIF4E or eIF(iso)4E genes can confer viral resistance against potyviruses in plants.
eIF4E is the main target of viruses in plants as well as humans. Are there any humans with gene variants of the eIF4E gene or any other genes, and does this make them less susceptible to certain viral infections? Furthermore, as the results for engineered viral resistance in plants are promising, could viruses that substantially affect humans be attenuated similarly and/or could humans be engineered to have viral resistance?
 Saha, Shreya, and Kristiina Mäkinen. "Insights into the Functions of eIF4E-Biding Motif of VPg in Potato Virus A Infection." Viruses, 12.2, 2020, pp. 197.
 Ruffel, Sandrine, et al. "A natural recessive resistance gene against potato virus Y in pepper corresponds to the eukaryotic initiation factor 4E (eIF4E)." The Plant Journal, 32.6, 2002, pp. 1067-1075.
 Montero, Hilda, Rebeca García-Román, and Silvia I. Mora. "eIF4E as a control target for viruses." Viruses, 7.2, 2015, pp. 739-750.
 Lellis, Andrew D., et al. "Loss-of-susceptibility mutants of Arabidopsis thaliana reveal an essential role for eIF (iso) 4E during potyvirus infection." Current Biology, 12.12, 2002, pp. 1046-1051.
Synthetic Genome Recoding
George Church proposes that it would be possible to make cells resistant to viruses through a process called recoding. It could enable the construction of organisms with unambiguous alternative genetic codes. A specific codon can be replaced with a synonymous one in the degenerate 64-codon genetic code (Plotkin and Kudla 2011). Done globally with corresponding tRNA removal, this entirely removes a codon from the genome, allowing reassignment for another use (which may be no use). Recoded cells with specific tRNAs removed or used for a novel amino acid should be broadly resistant to decoding infective nucleic acid messages, such as from viruses. For example, a bacterial strain that cannot recognize a common sense codon should be unable to translate essentially any phage gene. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849531/
by Darko Savic on Aug 04, 2020