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Searching for Relatives of SARS-Cov-2 in Bats RESEARCH HIGHLIGHTS IN BRIEF PUBLIC HEALTH Defeating dengue with Wolbachia The introduction of Wolbachia bacteria into Aedes aegypti mos- quitoes confers resistance to dengue virus (DENV) and other BROOK/ ROBERT Credit: LIBRARY/Alamy PHOTO SCIENCE arbovirues, and the release of Wolbachia- infected mosquitoes SYNTHETIC BIOLOGY in endemic regions may be an effective arboviral control strat- egy. Now, Utarini et al. report the results a cluster-randomized trial involving the release of A. aegypti mosquitoes infected with the wMel strain of Wolbachia pipientis for the control of DENV Designer bacteria infections in Yogyakarta, Indonesia. Geographical clusters ran- domly received either deployments of wMel- infected A. aegypti (interventional clusters) or no deployments (control clusters), Engineering bacteria by removing code of viral genomes. Cells were and virologically confirmed dengue (VCD) was surveyed in sense codons and their cognate treated with a cocktail of phages 8,144 patients from 18 primary care clinics. In the control clus- tRNAs could lead to the creation containing the phages lambda, ters, VCD occurred in 9.4% of patients but remarkably DENV of cells with desirable properties P1vir, T4, T6 and T7, which have was detected in only 2.3% of patients in interventional clusters. for biotechnology applications, such TCA or TCG sense codons that are The incidence of symptomatic dengue fever and hospitaliza- tions for VCD was significantly reduced in interventional clus- as complete resistance to contami- 10–58 times more abundant than the ters, suggesting that mosquito deployments could eliminate nating phages or the ability to incor- TAG codon in their genomes, and Ser dengue fever in endemic regions. porate noncanonical amino acids observed that cells lacking tRNA CGA Ser ORIGINAL article Utarini, A. et al. Efficacy of Wolbachia- infected mosquito (ncAAs) during translation, resulting and tRNA UGA (but not RF1 alone) deployments for the control of dengue. N. Engl. J. Med. 384, 2177–2186 (2021) in the synthesis of novel non-natural were resistant to phage-induced lysis, VIRAL EVOLUTION heteropolymers. Previous work suggesting that the deletion of those led to the creation of a strain of tRNAs confers resistance to a broad Searching for relatives of SARS-CoV-2 in bats Escherichia coli (Syn61) with a range of phages. Coronaviruses (CoVs) that are close relatives of severe acute res- synthetic recoded genome in which The authors also demonstrated piratory syndrome coronavirus 2 (SARS-CoV-2) have been found two sense codons (serine TCG and how assigning ncAAs to TCG, in bats and pangolins, yet the evolutionary history of SARS-CoV-2 TCA) and the amber stop codon TCA and TAG in Syn61Δ3 could is unclear. Zhou et al. report the discovery of bat CoVs from Yunnan province, China, that are closely related to SARS-CoV-2, TCA were replaced with synonymous be used to incorporate ncAAs at including a virus that displays high sequence identity to codons, such that Syn61 uses only specific sites in biopolymers. Using SARS- CoV-2 in most genomic regions. The authors performed 61 of the 64 available codons. In a tyrosyl-tRNA synthetase–tRNA metagenomic sequencing on 411 bat samples and assembled recent study, Chin and colleagues and pyrrolysyl-tRNA synthetase– 24 CoV metagenomes, including four SARS-CoV-2- related evolved Syn61 and removed the tRNA pairs, the authors were able viruses. The closest relative to SARS-CoV-2 was Rhinolophus tRNAs and the translation release to reassign the TCG, TCA and pusillus virus RpYN06, which has 94.5% sequence identity and, in some genes, has the highest similarity to SARS-CoV-2 identified factor that decode the TCG, TCA TAG codons for specific ncAA thus far. However, the spike gene has a much lower sequence and TAG codons, leading to complete incorporation into biopolymers. identity, suggestive of a genomic recombination event, making resistance to a cocktail of phages Two different ncAAs were RpYN06 the second closest relative of SARS-CoV-2 identified and the encoded incorporation of incorporated at three different to date after the bat CoV RaTG13, highlighting the potentially ncAAs during ribosome-mediated locations, and three distinct ncAAs complex evolutionary history of SARS-CoV-2. biosynthesis. were simultaneously incorporated ORIGINAL article Zhou, H. et al. Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses. Cell https://doi.org/10.1016/ The authors hypothesized into a ribosome-produced j.cell.2021.06.008 (2021) that replacement of TCG, TCA biopolymer in Syn61Δ3 cells. and TAG codons in the Syn61 Furthermore, the authors were CELLULAR MICROBIOLOGY genome would enable the deletion able to encode the synthesis of Ser Ser Evolution of a viral nucleocapid of tRNA CGA, tRNA UGA and noncanonical hexamers and Evolutionary theory on the origin of viruses suggests that release factor 1 (RF1) that decode octamers as protein fusions, as well primordial replicators recruited host proteins for virion these codons. Deletion of genes as the synthesis of a non-natural formation. In a recent study, Tetter et al. evolved a bacterial that encode these tRNAs and RF1 macrocycle that resembles the enzyme that does not have an inherent affinity for nucleic led to the creation of a new strain products of non-ribosomal peptide acids into a virus-like nucleocapsid protein that efficiently (Syn61Δ3), confirming that these synthetases. packages and encapsidates copies of its own mRNA. Starting with the multimeric cage-forming protein lumazine synthase genes could be deleted; however, This study highlights the potential from Aquifex aeolicus, the authors performed a series of the strain experienced growth of sense codon reassignment in evolutionary experiments leading to the artificial nucleocapsid. defects. Through random parallel bacteria to generate phage-resistant Cryo- electron microscopy of the evolutionary intermediates mutagenesis and selection, the strains and designer proteins with a and the final design revealed a structural evolution towards authors created a Syn61Δ3 variant range of applications. a virus-like architecture through protomer reorganization. that grew significantly faster. Furthermore, evolution led to highly specific virus-like RNA Ashley York Next, the authors investigated packaging mediated by secondary RNA stem-loop structures, ORIGINAL article Robertson, W. E. et al. and protection from external nucleases. how tRNA and RF1 deletion affected Sense codon reassignment enables viral resistance and encoded polymer synthesis. Science 372, ORIGINAL article Tetter, S. et al. Evolution of a virus-like architecture and packaging phage infection, which relies on the 1057–1062 (2021) mechanism in a repurposed bacterial protein. Science 372, 1220–1224 (2021) cell decoding the canonical genetic 482 | AUGUST 2021 | VOLUME 19 www.nature.com/nrmicro 0123456789();: .
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