M2-2 gene as a new alternative molecular marker for phylogenetic, phylodynamic, and evolutionary studies of hRSV

Nunes, Denis Bruno S M; Vieira, Camila; Sá, Jéssica Maróstica de; Araujo, Gabriela Campos de; Caruso, Ícaro Putinhon; Souza, Fátima P.

doi:10.1016/j.virusres.2022.198850

Cited by 3 publications

(2 citation statements)

References 46 publications

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“…Whole genome sequencing has more recently been reported as an alternative method for genotyping, and it has been shown to better represent RSV genotypes in the population (30)(31)(32)(33). M2-2 sequencing has also been proposed as an alternative genotyping method, as this is one of the smallest viral proteins with a low level of conservation (34). Notably, no current routine genotyping method focuses on the viral polymerase and its associated genes, despite the critical role of these proteins in viral replication and infection.…”

Section: Introductionmentioning

confidence: 99%

Identification of distinct genotypes in circulating RSV A strains based on variants on the virus replication-associated genes

Musa,

Faber,

Forrest

et al. 2024

Preprint

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Respiratory syncytial virus is a common cause of respiratory infection that often leads to hospitalization of infected younger children and older adults. RSV is classified into two strains, A and B, each with several subgroups or genotypes. One issue with the definition of these subgroups is the lack of a unified method of identification or genotyping. We propose that genotyping strategies based on the genes coding for replication-associated proteins could provide critical information on the replication capacity of the distinct subgroup, while clearly distinguishing genotypes. Here, we analyzed the virus replication-associated genes N, P, M2, and L from de novo assembled RSV A sequences obtained from 31 newly sequenced samples from hospitalized patients in Philadelphia and 78 additional publicly available sequences from different geographic locations within the US. In-depth analysis and annotation of the protein variants in L and the other replication-associated proteins N, P, M2-1, and M2-2 identified the polymerase protein L as a robust target for genotyping RSV subgroups. Importantly, our analysis revealed non-synonymous variations in L that were consistently accompanied by conserved changes in its co-factor P or the M2-2 protein, suggesting associations and interactions between specific domains of these proteins. These results highlight L as an alternative to other RSV genotyping targets and demonstrate the value of in-depth analyses and annotations of RSV sequences as it can serve as a foundation for subsequent in vitro and clinical studies on the efficiency of the polymerase and fitness of different virus isolates.

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Section: Introductionmentioning

confidence: 99%

Identification of distinct genotypes in circulating RSV A strains based on variants on the virus replication-associated genes

Musa,

Faber,

Forrest

et al. 2024

Preprint

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“…The human RSV genome codifies 10 ORFs and 11 proteins, of which the most studied ones are the attachment glycoprotein (G) and the fusion protein (F), which are both associated with the initial phases of infection. Two main variants (A and B) with several genotypes and subgenotypes circulate simultaneously [3][4][5]. According to the classification proposed by Goya et al, based on the phylogeny of the G protein, three genotypes have been defined for RSV-A and seven for RSV-B, as well as several subgenotypes [6,7].…”

Section: Introductionmentioning

confidence: 99%

The Modification of the Illumina® CovidSeq™ Workflow for RSV Genomic Surveillance: The Genetic Variability of RSV during the 2022–2023 Season in Northwest Spain

Davina-Nunez,

Perez-Castro,

Cabrera-Alvargonzalez

et al. 2023

IJMS

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There is growing interest in the molecular surveillance of the Respiratory Syncytial Virus and the monitorization of emerging mutations that could impair the efficacy of antiviral prophylaxis and treatments. A simple, scalable protocol for viral nucleic acid enrichment could improve the surveillance of RSV. We developed a protocol for RSV-A and B amplification based on the Illumina CovidSeq workflow using an RSV primer panel. A total of 135 viral genomes were sequenced from nasopharyngeal samples through the optimization steps of this panel, while an additional 15 samples were used to test the final version. Full coverage of the G gene and over 95% of the coverage of the F gene, the target of the available RSV antivirals or monoclonal antibodies, were obtained. The F:K68N mutation, associated with decreased nirsevimab activity, was detected in our facility. Additionally, phylogenetic analysis showed several sublineages in the 2022–2023 influenza season in Europe. Our protocol allows for a simple and scalable simultaneous amplification of the RSV-A and B whole genome, increasing the yield of RSV sequencing and reducing costs. Its application would allow the world to be ready for the detection of arising mutations in relation to the widespread use of nirsevimab for RSV prevention.

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Identification of distinct genotypes in circulating RSV A strains based on variants in the virus replication-associated genes

Musa,

Faber,

Forrest

et al. 2024

J Virol

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Respiratory syncytial virus (RSV) is a common cause of respiratory infection that often leads to hospitalization of infected younger children and older adults. RSV is classified into two strains, A and B, each with several subgroups or genotypes. One issue with the definition of these subgroups is the lack of a unified method of identification or genotyping. We propose that genotyping strategies based on the genes coding for replication-associated proteins could provide critical information on the replication capacity of the distinct subgroups, while clearly distinguishing genotypes. Here, we analyzed the virus replication-associated genes N, P, M2, and L from de novo assembled RSV A sequences obtained from 31 newly sequenced samples from hospitalized patients in Philadelphia and 78 additional publicly available sequences from different geographic locations within the United States. In-depth analysis and annotation of variants in the replication-associated proteins identified the polymerase protein L as a robust target for genotyping RSV subgroups. Importantly, our analysis revealed non-synonymous variations in L that were consistently accompanied by conserved changes in its co-factor P or the M2-2 protein, suggesting associations and interactions between specific domains of these proteins. Similar associations were seen among sequences of the related human metapneumovirus. These results highlight L as an alternative to other RSV genotyping targets and demonstrate the value of in-depth analyses and annotations of RSV sequences as it can serve as a foundation for subsequent in vitro and clinical studies on the efficiency of the polymerase and fitness of different virus isolates. IMPORTANCE Given the historical heterogeneity of respiratory syncytial virus (RSV) and the disease it causes, there is a need to understand the properties of the circulating RSV strains each season. This information would benefit from an informative and consensus method of genotyping the virus. Here, we carried out a variant analysis that shows a pattern of specific variations among the replication-associated genes of RSV A across different seasons. Interestingly, these variation patterns, which were also seen in human metapneumovirus sequences, point to previously defined interactions of domains within these genes, suggesting co-variation in the replication-associated genes. Our results also suggest a genotyping strategy that can prove to be particularly important in understanding the genotype-phenotype correlation in the era of RSV vaccination, where selective pressure on the virus to evolve is anticipated. More importantly, the categorization of pneumoviruses based on these patterns may be of prognostic value.

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M2-2 gene as a new alternative molecular marker for phylogenetic, phylodynamic, and evolutionary studies of hRSV

Cited by 3 publications

References 46 publications

Identification of distinct genotypes in circulating RSV A strains based on variants on the virus replication-associated genes

Identification of distinct genotypes in circulating RSV A strains based on variants on the virus replication-associated genes

The Modification of the Illumina® CovidSeq™ Workflow for RSV Genomic Surveillance: The Genetic Variability of RSV during the 2022–2023 Season in Northwest Spain

Identification of distinct genotypes in circulating RSV A strains based on variants in the virus replication-associated genes

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