Decoding VZV’s evolutionary arsenal: how Beijing strains use recombination and adaptive mutations to thrive

Varicella-zoster virus (VZV), a highly contagious α-herpesvirus, causes chickenpox and shingles. Although vaccines have been widely deployed, breakthrough infections still occur occasionally. Therefore, genomic surveillance of VZV remains essential. This study collected samples from 28 VZV-infected patients in Beijing, generating 25 complete viral genome sequences. These strains exhibited high genomic similarity and all belonged to Clade 2, which we further subdivided into five subclades with distinct characteristic variants. Most newly sequenced strains carried the A20795T (gC: Ser107Thr) mutation and were classified as Clade 2b.4. Recombination analysis identified 32 putative recombination events, including both inter- and intra-clade types. Genes with diverse functions are under differential selective pressures, with 3-20 positively selected sites detected in <i>ORF17</i>, <i>ORF33</i>, <i>ORF33.5</i>, and <i>ORF14</i> (gC). These findings on new subclades, frequent recombination, and rapidly changing genes crucial for viral adaptation are important for controlling future outbreaks and improving vaccine effectiveness. The research provided critical resources for investigating VZV genomic evolution in Beijing and to offer new insights into viral evolution and transmission patterns for public health initiatives.