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This comprehensive review synthesizes current knowledge on HCMV pathogenesis, prevention, and treatment strategies. We examine the molecular mechanisms of HCMV entry, focusing on the structure and function of key envelope glycoproteins (gB, gH\/gL\/gO, gH\/gL\/pUL128-131) and their interactions with cellular receptors such as PDGFR\u03b1, NRP2, and THBD. The review explores HCMV\u2019s sophisticated immune evasion strategies, including interference with pattern recognition receptor signaling, modulation of antigen presentation, and regulation of NK and T cell responses. We highlight recent advancements in developing neutralizing antibodies, various vaccine strategies (live-attenuated, subunit, vector-based, DNA, and mRNA), antiviral compounds (both virus-targeted and host-targeted), and emerging cellular therapies such as TCR-T cell approaches. By integrating insights from structural biology, immunology, and clinical research, we identify critical knowledge gaps and propose future research directions. This analysis aims to stimulate cross-disciplinary collaborations and accelerate the development of more effective prevention and treatment strategies for HCMV infections, addressing a significant unmet medical need.<\/jats:p>","DOI":"10.1186\/s43556-024-00226-7","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T02:14:58Z","timestamp":1732500898000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Human cytomegalovirus: pathogenesis, prevention, and treatment"],"prefix":"10.1186","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9062-0999","authenticated-orcid":false,"given":"Zifang","family":"Shang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"issue":"5","key":"226_CR1","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1111\/j.1462-5822.2012.01774.x","volume":"14","author":"F Goodrum","year":"2012","unstructured":"Goodrum F, Caviness K, Zagallo P. 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