Molecular Evolution of the Fusion Protein (F) Gene in Human Respirovirus 3

Abstract

To elucidate the evolution of human respirovirus 3 (HRV3), we performed detailed genetic analyses of the F gene (full-length) detected from hundreds of HRV3 strains obtained from various geographic regions. First, we performed time-scaled evolutionary analyses using the Bayesian Markov chain Monte Carlo method. Then, we performed analyses of phylodynamics, similarity, phylogenetic distance, selective pressure, and conformational B-cell epitope with the F-protein structural analyses. Time-scaled phylogenetic tree showed that the common ancestor of HRV3 and bovine respirovirus 3 diverged over 300 years ago and subdivided it into three major clusters and four subclusters during the most recent 100 years. The overall evolutionary rate was approximately 10 −3 substitutions/site/year. Indigenous similarity was seen in the present strains, and the mean phylogenetic distance were 0.033. Many negative selection sites were seen in the ectodomain. The conformational epitopes did not correspond to the neutralizing antibody binding sites. These results suggest that the HRV3 F gene is relatively conserved and restricted in this diversity to preserve the protein function, although these strains form many branches on the phylogenetic tree. Furthermore, HRV3 reinfection may be responsible for discordances between the conformational epitopes and the neutralizing antibody binding sites of the F protein. These findings contribute to a better understanding of HRV3 virology.

Divergent Viruses Discovered in Swine Alter the Understanding of Evolutionary History and Genetic Diversity of the Respirovirus Genus and Related Porcine Parainfluenza Viruses

“…We attempted to reconstruct the evolutionary history of species within the Respirovirus genus, inferred that Respirovirus genus may have originated from 636AD (95% HPD = 214 AD to 951 AD). We evaluated the time signal through DRT to verify the reliability of tMRCA, and the estimated divergence time of BPIV-3 and HPIV-3 was close to other reports ( 57 , 58 ). Interestingly, negative-sense RNA (NSV) viruses are commonly under purifying selection (consistent with our result about selection analysis of PPIV-1), which may mask an ancient evolutionary history, resulting in an underestimation of the time of origin ( 55 ).…”

Detailed Evolutionary Analyses of the F Gene in the Respiratory Syncytial Virus Subgroup A

“…The evolutionary rate of the RSV-A F gene was estimated as 7.69 × 10 −4 substitutions/site/year (s/s/y) (95% HPD, 7.10-8.29 × 10 −4 s/s/y). This value was similar to the F gene of human respirovirus type 3 [42]. Moreover, the rate was slower than that of the attachment glycoprotein (G) gene (another major antigen) [21].…”

“…As a result, conformational epitopes did not correspond to the NT-Ab binding sites in the prefusion type of the protein. The results suggested that this mismatch may be partially responsible for RSV reinfection and another virus such as human respiro-virus type 3 [42]. Furthermore, an amino acid substitution of N276S in the palivizumab binding sites may reduce this drug effect.…”

One year into the pandemic: Short-term evolution of SARS-CoV-2 and emergence of new lineages

“…4 Relationships between amino acid substitutions and conformational epitopes in the SARS-CoV-2 spike proteins. Conformational epitope may induce the neutralizing antibody against various viruses ( Aso et al, 2019 ). Therefore, to estimate the vaccine's efficacy, the relationships between conformational epitopes and amino acid substitutions of the S protein in the B.1.1.7 and B.1.351 lineages were examined.…”

“…Therefore, to estimate the vaccine's efficacy, the relationships between conformational epitopes and amino acid substitutions of the S protein in the B.1.1.7 and B.1.351 lineages were examined. Detailed procedures of these examinations were made as previously described ( Aso et al, 2019 ). The changes detected in the two lineages (red) affected partially overlapping epitopes (blue).…”