Evolutionary phylogeography reveals novel genotypes of coxsackievirus A24 variant and updates the spatiotemporal dynamics in the population with acute hemorrhagic conjunctivitis

• Published in: International journal of infectious diseases 2022-11, Vol.124, p.227-239
• Main Authors: Chen, Peng, Lin, Xiao-Juan, Ji, Feng, Li, Yan, Wang, Su-Ting, Liu, Yao, Tao, Ze-Xin, Xu, Ai-Qiang
• Format: Article
• Language: English
• Subjects: Acute hemorrhagic conjunctivitis; Coxsackievirus A24 variant; Natural selection; Phylogeny; Phylogeography
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2022.10.007

•Eight coxsackievirus A24 variant (CVA24v) genotypes were divided, and two novel genotypes were reported first.•Five genotypes of CVA24v circulated previously in mainland China.•Special ocular tropism might impact the variation of CVA24v.•Residue 146T could contribute to the CVA24v outbreaks and its pathogenicity.•CVA24v possesses a potential neuroinvasion capability besides causing acute hemorrhagic conjunctivitis. The coxsackievirus A24 variant (CVA24v) has raised a remarkable concern because of its main etiological role in acute hemorrhagic conjunctivitis. We conducted a retrospective study to summarize CVA24v isolated from acute hemorrhagic conjunctivitis outbreaks and acute flaccid paralysis surveillance in Shandong province, China during 1988-2020. Phylogenetic and phylogeographic methods based on the VP1 coding region were used to determine the CVA24v origin, spatiotemporal dynamics, and evolution. Also, the positive selection sites in the VP1 gene were identified and exhibited in the tertiary structure. The global CVA24vs were classified into eight genotypes (GⅠ-GⅧ). Here, 12 CVA24v isolates were detected, of which five strains were typed as two novel genotypes (GⅦ and GⅧ) and reported first in the world. The time to the most recent common ancestor of the global CVA24v was estimated around March 1965 and evolved with 5.573 × 10−3 substitutions/site/year. Four residues under positive selection were detected, and residue 146T might be adapted in the CVA24v pandemic. Phylogeographic analysis indicated that China was the main source sink for CVA24v dispersion in a long-lasting global pattern. Our study updated the epidemiological characteristics of CVA24v and enabled a better understanding of the molecular mechanism underlying different genotypes. The results provided new insights into the CVA24v origin, spatiotemporal dynamics, and possibly, the determinants of viral tropism and pathogenicity. [Display omitted]