The human cytomegalovirus chemokine binding protein UL22A is necessary for efficient reactivation from latency in CD34(+) hematopoietic progenitor cells and humanized mice
Summary
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that infects 60%-90% of the population worldwide. In immunocompetent individuals, primary infection is asymptomatic and results in lifelong latent infection in CD34+ hematopoietic progenitor cells. Viral reactivation remains a major complication for immunosuppressed individuals, but current therapeutics targeting HCMV replication show significant toxicity. Thus, a better understanding of the mechanisms controlling latency and reactivation is necessary to develop new therapeutics targeting these stages of the HCMV lifecycle. UL22A is a chemokine-binding protein encoded by HCMV. Viral chemokine-binding proteins help regulate the host immune response and promote virus replication. We show that UL22A and its Y65 and Y69 residues are necessary for reactivation from latency in CD34+ hematopoietic progenitor cells and in a humanized mouse model. Additionally, we show that UL22A binding to its only known chemokine partner, RANTES (regulated on activation, normal T cell expressed and secreted), is not necessary for this reactivation phenotype. These findings suggest other novel functions for UL22A that we do not yet understand.
| Authors | Turner RL, Diggins NL, Slind L, Mitchell J, Pham AH, Parkins CJ, Perez W, Medica S, Denton M, Andoh TF, Webb GM, Andrade-Vera D, Streblow DN, Caposio P, Hancock MH |
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| Journal | Journal of virology |
| Publication Date | 2026 Aug 18;100(8):e0061226 |
| PubMed | 42505120 |
| PubMed Central | PMC13483475 |
| DOI | 10.1128/jvi.00612-26 |