Emergence of Lineage E.4 and Structural Plasticity of A28L Protein in Mpox Virus: Characterization of LCR7 Length Polymorphisms Across Lineages — Shenzhen City, Guangdong Province, China, 2023–2025
Jul 2026· China CDC Weekly· Vol 8, pp. 847 - 851· 0 citations
Medicine
TL;DR
Structural variation in A28L provides additional insight into MPXV evolution beyond conventional single-nucleotide analyses, and continued surveillance of these genomic features may improve monitoring of viral transmission and the emergence of new variants.
Abstract
What is already known about this topic? The A28L protein is involved in mpox virus (MPXV) attachment and fusion, is a major target of neutralizing antibodies, and contains regions prone to genetic variation. What is added by this report? Analysis of 6,834 global and 260 Shenzhen MPXV genomes identified lineage-specific length polymorphisms in the A28L low-complexity region (LCR7). Emerging E.4 viruses exhibited complex deletion patterns and a characteristic OPG153_E293Q substitution, indicating ongoing structural diversification. What are the implications for public health practice? Structural variation in A28L provides additional insight into MPXV evolution beyond conventional single-nucleotide analyses. Continued surveillance of these genomic features may improve monitoring of viral transmission and the emergence of new variants.
Combined genomic surveillance and structural analyses demonstrated that the investigated Omicron-associated mutations largely preserved the overall architecture of the M protein-Fab interaction interface while modulating residue-level energetic contributions and the conformational dynamics of the E protein.
Simple Summary Porcine epidemic diarrhea virus (PEDV) continues to cause severe watery diarrhea and devastating piglet production losses worldwide. To map the long-term evolutionary trends of the virus in Thailand, this study evaluated clinical samples collected over a 16-year period (2008–2024) using a comprehensive molecular and bioinformatic pipeline. By analyzing the predicted full-length spike (S) protein structures modeled from nucleotide sequences, we tracked critical mutational shifts and predicted antigenic variation within major neutralizing domains (including COE, SS2, SS6, and 2C10) that may influence antibody recognition. The findings reveal the emergence of unique insertion/deletion (InDel) strains and establish that primitive Thai strains (Cluster 1) likely represent the original structural template of PEDV in the region prior to subsequent divergence into G1 and G2b-related lineages. Ultimately, this framework bridges genomic evolution with structural biology, providing essential data to guide vaccine selection, optimize planned exposure protocols, and update swine biosecurity strategies.
C. Stott, Tanakamol Mahawan, P. Piñeyro et al.· Animals· 0 citations
Higher order protein structural predictions suggested that the putative epistatic interactions among E180V, G184V, and G252V, D253G may be associated with S protein folding and structural stability.
M. Jogi, Sristy Shikha, Pushpendra Singh et al.· Frontiers in Immunology· 0 citations
The identification of a novel A2–B3 recombinant lineage provides evidence of ongoing viral evolution through recombination, a mechanism that may alter transmissibility, virulence, or immune responses, and underscores the importance of whole-genome surveillance for accurate viral characterization.
A. Fall, C. Morris, O. Elgazayerly et al.· Microbiology spectrum· 0 citations
Background Human metapneumovirus (hMPV) is a leading cause of acute respiratory infections worldwide, yet whole-genome surveillance data remain scarce in eastern China. The evolutionary dynamics of G gene duplication variants and their molecular drivers are poorly characterized. Methods From 2024 to 2025, we conducted prospective hMPV surveillance in Nantong, Jiangsu Province, screening 1,602 respiratory specimens by multiplex qPCR. Complete whole-genome sequences were obtained from 26 of 27 positive strains via probe-capture next-generation sequencing, and integrated with 574 global reference genomes. G gene duplication variants (111nt_dup/180nt_dup) were characterized, O-glycosylation sites predicted (NetOGlyc 4.0), and Bayesian phylodynamic analysis (BEAST v1.10.4) performed on the 111nt_dup lineage. Results The overall detection rate was 1.7% (27/1,602), with the highest burden in children aged 0–5 years (3.6%) and peak circulation in winter and spring. Phylogenetic analysis revealed a sharp genotype shift among the sequenced strains—from A2.2.2 in 2024 to B2 in 2025 (12/12 vs. 0/14; p < 0.001, Fisher’s exact test)—concordant with contemporaneous observations in Shanghai and Beijing. Globally, 111nt_dup prevalence rose from <10% before 2015 to >90% by 2025 (Cochran-Armitage trend test, p = 6.86 × 10−7), whereas 180nt_dup disappeared after 2021. The 111nt_dup lineage displayed near-complete fixation of serine at G protein position 90 (S90, 98.9% vs. 0% in 180nt_dup; p < 0.001). S90 frequency and 111nt_dup prevalence rose in tight synchrony (Pearson’s r > 0.95). Bayesian Skyline analysis showed a pandemic-associated population bottleneck (2020–2021) followed by rapid recovery to pre-pandemic levels by late 2022. Conclusion The global dominance of 111nt_dup is better explained by lineage-specific molecular selection than neutral drift. Co-occurrence of the 111nt_dup with the predicted S90 O-glycosylation site suggests a model in which predicted glycosylation-driven optimization of the G protein mucin-like domain may enhance fitness, with implications for hMPV vaccine strain surveillance.
Xiaolei Ji, Zhen-Zhen Liu, X. Cai et al.· Frontiers in Microbiology· 0 citations
Findings reveal a viral trade-off: the mutation attenuates epithelial replication and immunopathology but enhances DC uptake and disables mucosal immune functions, a strategy that likely contributed to the global predominance of PA-X N193S mutation in epidemic H5 subtype viruses.
X. Miao, Xing Xu, Yixuan Han et al.· Emerging Microbes and Infect...· 0 citations
