Murine cytomegalovirus m119-118 encodes a new viral Fc receptor antagonizing host Fc receptor activation
- 1Leibniz Institute of Virology (LIV)
Abstract
Cytomegaloviruses (CMVs) encode numerous immunomodulatory proteins to counteract innate and adaptive immunity. One class of immune evasion proteins is viral Fc receptors (vFcRs), which bind to the Fc region of IgG antibodies and interfere with antibody-mediated effector functions crucial for antiviral defense. Despite the established role of vFcRs in modulating antibody-mediated immunity, their contribution to viral pathogenesis in vivo remains incompletely understood. Although human CMV (HCMV) encodes four vFcRs, only a single vFcR, fcr-1 encoded by gene m138, has been identified in murine CMV (MCMV). By comparing and cloning the genomes of MCMV strains v70, K181+, and K181Perth, we identified a frameshift mutation affecting the spliced m119-118 transcript in K181Perth. This finding prompted us to investigate the function of the m119-118 gene. We show that it encodes a second MCMV vFcR, which we named fcr-2. It is structurally similar to its positional homolog in HCMV, UL119-118/gp68, and binds specifically to the Fc part of murine IgG. Deletion of both vFcRs genes from the MCMV genome resulted in substantially reduced Fc-binding to the surface of infected cells, indicating a complementary function of the vFcRs. Functional assays with viral deletion mutants further demonstrated that both proteins inhibit host Fc receptor activation in a cooperative fashion. Although an m119-118-deficient MCMV was only marginally attenuated in infected BALB/c mice, an m119-118 and m138 double mutant attained significantly lower organ titers than the m138-deficient mutant. These data suggest an important cooperative function of the two MCMV vFcRs for viral dissemination and pathogenesis in vivo.
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BibTeX
@misc{staliunaite2026murine,
title = {{Murine cytomegalovirus m119-118 encodes a new viral Fc receptor antagonizing host Fc receptor activation}},
author = {L. Staliunaite and M. Mellin and E. Ostermann and K. Ehrhardt and B. Chan and A. J. Redwood and A. J. Davison and F. R. Stahl and P. Kolb and H. Hengel and W. Brune},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.758151},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.758151v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Murine cytomegalovirus m119-118 encodes a new viral Fc receptor antagonizing host Fc receptor activation
AU - L. Staliunaite
AU - M. Mellin
AU - E. Ostermann
AU - K. Ehrhardt
AU - B. Chan
AU - A. J. Redwood
AU - A. J. Davison
AU - F. R. Stahl
AU - P. Kolb
AU - H. Hengel
AU - W. Brune
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.758151
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.758151v1
AB - Cytomegaloviruses (CMVs) encode numerous immunomodulatory proteins to counteract innate and adaptive immunity. One class of immune evasion proteins is viral Fc receptors (vFcRs), which bind to the Fc region of IgG antibodies and interfere with antibody-mediated effector functions crucial for antiviral defense. Despite the established role of vFcRs in modulating antibody-mediated immunity, their contribution to viral pathogenesis in vivo remains incompletely understood. Although human CMV (HCMV) encodes four vFcRs, only a single vFcR, fcr-1 encoded by gene m138, has been identified in murine CMV (MCMV). By comparing and cloning the genomes of MCMV strains v70, K181+, and K181Perth, we identified a frameshift mutation affecting the spliced m119-118 transcript in K181Perth. This finding prompted us to investigate the function of the m119-118 gene. We show that it encodes a second MCMV vFcR, which we named fcr-2. It is structurally similar to its positional homolog in HCMV, UL119-118/gp68, and binds specifically to the Fc part of murine IgG. Deletion of both vFcRs genes from the MCMV genome resulted in substantially reduced Fc-binding to the surface of infected cells, indicating a complementary function of the vFcRs. Functional assays with viral deletion mutants further demonstrated that both proteins inhibit host Fc receptor activation in a cooperative fashion. Although an m119-118-deficient MCMV was only marginally attenuated in infected BALB/c mice, an m119-118 and m138 double mutant attained significantly lower organ titers than the m138-deficient mutant. These data suggest an important cooperative function of the two MCMV vFcRs for viral dissemination and pathogenesis in vivo.
ER -