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.

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.