Otero Claire E, Petkova Sophia, Ebermann Martin, Taher Husam, John Nessy, Hoffmann Katja, Davalos Angel, Moström Matilda J, Gilbride Roxanne M, Papen Courtney R, Barber-Axthelm Aaron, Scheef Elizabeth A, Barfield Richard, Sprehe Lesli M, Kendall Savannah, Manuel Tabitha D, Beechwood Teresa, Nguyen Linh Khanh, Vande Burgt Nathan H, Chan Cliburn, Denton Michael, Streblow Zachary J, Streblow Daniel N, Tarantal Alice F, Hansen Scott G, Kaur Amitinder, Permar Sallie, Früh Klaus, Hengel Hartmut, Malouli Daniel, Kolb Philipp
Department of Pediatrics, Weill Cornell Medicine, New York, New York, USA.
Department of Pathology, Duke University, Durham, North Carolina, USA.
Nat Commun. 2025 Jan 31;16(1):1200. doi: 10.1038/s41467-025-56419-3.
Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation in vitro, but their role in infection and pathogenesis is unknown. To examine their in vivo function in an animal model evolutionarily closely related to humans, we identified and characterized Rh05, Rh152/151 and Rh173 as the complete set of vFcγRs encoded by rhesus CMV (RhCMV). Each one of these proteins displays functional similarities to their prospective HCMV orthologs with respect to antagonizing host FcγR activation in vitro. When RhCMV-naïve male rhesus macaques were infected with vFcγR-deleted RhCMV, peak plasma DNAemia levels and anti-RhCMV antibody responses were comparable to wildtype infections of both male and female animals. However, the duration of plasma DNAemia was significantly shortened in immunocompetent, but not in CD4 + T cell-depleted animals. Since vFcγRs were not required for superinfection of rhesus macaques, we conclude that these proteins can prolong lytic replication during primary infection by evading virus-specific adaptive immune responses, particularly antibodies.
人巨细胞病毒(HCMV)编码四种病毒Fc-γ受体(vFcγRs),它们在体外可抵消抗体介导的激活作用,但其在感染和发病机制中的作用尚不清楚。为了在与人类进化关系密切的动物模型中研究它们的体内功能,我们鉴定并表征了Rh05、Rh152/151和Rh173,它们是恒河猴巨细胞病毒(RhCMV)编码的完整vFcγR集。这些蛋白质中的每一种在体外拮抗宿主FcγR激活方面都与其预期的HCMV直系同源物表现出功能相似性。当未感染RhCMV的雄性恒河猴感染缺失vFcγR的RhCMV时,血浆DNA血症峰值水平和抗RhCMV抗体反应与雄性和雌性动物的野生型感染相当。然而,有免疫能力的动物血浆DNA血症持续时间显著缩短,但CD4 + T细胞耗竭的动物则不然。由于vFcγRs对于恒河猴的再次感染不是必需的,我们得出结论,这些蛋白质可以通过逃避病毒特异性适应性免疫反应,特别是抗体,在初次感染期间延长裂解复制。