Identification and functional characterization of a novel Fc gamma-binding glycoprotein in rhesus cytomegalovirus

Philipp Kolb, Steven Sijmons, Matthew R. McArdle, Husam Taher, Jennie Womack, Colette Hughes, Abigail Ventura, Michael A. Jarvis, Christiane Stahl-Hennig, Scott Hansen, Louis Picker, Daniel Malouli, Hartmut Hengel, Klaus Frueh

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Receptors recognizing the Fc part of immunoglobulin G (FcRs) are key determinants in antibody-mediated immune responses. Members of the Herpesviri-dae interfere with this immune regulatory network by expressing viral FcRs (vFcRs). Human cytomegalovirus (HCMV) encodes four distinct vFcRs that differ with respect to their IgG subtype specificity and their impact on antibody-mediated immune function in vitro. The impact of vFcRs on HCMV pathogenesis and immunomodulation in vivo is not known. The closest evolutionary animal model of HCMV is rhesus CMV (RhCMV) infection of rhesus macaques. To enable the characterization of vFcR function in this model, we studied IgG binding by RhCMV. We show that lysates of RhCMV-infected cells contain an IgG-binding protein of 30 kDa encoded by the gene Rh05 that is a predicted type I glycoprotein belonging to the RL11 gene family. Upon deletion of Rh05, IgG-Fc binding by RhCMV strain 68-1 is lost, whereas ectopic expression of Rh05 results in IgG binding to transfected cells consistent with Rh05 being a vFcR. Using a set of reporter cell lines stably expressing human and rhesus FcRs, we further demonstrate that Rh05 antagonizes host FcR activation. Compared to Rh05-intact RhCMV, RhCMVΔRh05 showed an increased activation of host FcR upon exposure of infected cells to IgG from RhCMV-seropositive animals, suggesting that Rh05 protects infected cells from opsonization and IgG-dependent activation of host FcRs. However, antagonizing host FcR activation by Rh05 was not required for the establishment and maintenance of infection of RhCMV, even in a seropositive host, as shown by the induction of T cell responses to heterologous antigens expressed by RhCMV lacking the gene region encoding Rh05. In contrast to viral evasion of natural killer cells or T cell recognition, the evasion of antibody-mediated effects does not seem to be absolutely required for infection or reinfection. The identification of the first vFcR that efficiently antagonizes host FcR activation in the RhCMV genome will thus permit more detailed studies of this immunomodulatory mechanism in promoting viral dissemination in the presence of natural or vaccine-induced humoral immunity.

Original languageEnglish (US)
Article numbere0207718
JournalJournal of virology
Volume93
Issue number4
DOIs
StatePublished - Feb 1 2019

Keywords

  • Antibody function
  • Cytomegalovirus
  • Fc receptors
  • Immune evasion
  • Immunology
  • Rhesus
  • Virology

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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  • Cite this

    Kolb, P., Sijmons, S., McArdle, M. R., Taher, H., Womack, J., Hughes, C., Ventura, A., Jarvis, M. A., Stahl-Hennig, C., Hansen, S., Picker, L., Malouli, D., Hengel, H., & Frueh, K. (2019). Identification and functional characterization of a novel Fc gamma-binding glycoprotein in rhesus cytomegalovirus. Journal of virology, 93(4), [e0207718]. https://doi.org/10.1128/JVI.02077-18