TY - JOUR
T1 - Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity
AU - Otero, Claire E.
AU - Petkova, Sophia
AU - Ebermann, Martin
AU - Taher, Husam
AU - John, Nessy
AU - Hoffmann, Katja
AU - Davalos, Angel
AU - Moström, Matilda J.
AU - Gilbride, Roxanne M.
AU - Papen, Courtney R.
AU - Barber-Axthelm, Aaron
AU - Scheef, Elizabeth A.
AU - Barfield, Richard
AU - Sprehe, Lesli M.
AU - Kendall, Savannah
AU - Manuel, Tabitha D.
AU - Beechwood, Teresa
AU - Nguyen, Linh Khanh
AU - Vande Burgt, Nathan H.
AU - Chan, Cliburn
AU - Denton, Michael
AU - Streblow, Zachary J.
AU - Streblow, Daniel N.
AU - Tarantal, Alice F.
AU - Hansen, Scott
AU - Kaur, Amitinder
AU - Permar, Sallie
AU - Früh, Klaus
AU - Hengel, Hartmut
AU - Malouli, Daniel
AU - Kolb, Philipp
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-025-56419-3
DO - 10.1038/s41467-025-56419-3
M3 - Article
C2 - 39885150
AN - SCOPUS:85217357762
SN - 2041-1723
VL - 16
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1200
ER -