title: Recombinant human cytomegalovirus (HCMV) RL13 binds human immunoglobulin G Fc.
abstract: The human cytomegalovirus (HCMV) protein RL13 has recently been described to be present in all primary isolates but rapidly mutated in culture adapted viruses. Although these data suggest a crucial role for this gene product in HCMV primary infection, no function has so far been assigned to this protein. Working with RL13 expressed in isolation in transfected human epithelial cells, we demonstrated that recombinant RL13 from the clinical HCMV isolates TR and Merlin have selective human immunoglobulin (Ig)-binding properties towards IgG1 and IgG2 subtypes. An additional Fc binding protein, RL12, was also identified as an IgG1 and IgG2 binding protein but not further characterized. The glycoprotein RL13 trafficked to the plasma membrane where it bound and internalized exogenous IgG or its constant fragment (Fcγ). Analysis of RL13 ectodomain mutants suggested that the RL13 Ig-like domain is responsible for the Fc binding activity. Ligand-dependent internalization relied on a YxxL endocytic motif located in the C-terminal tail of RL13. Additionally, we showed that the tyrosine residue could be replaced by phenylalanine but not by alanine, indicating that the internalization signal was independent from phosphorylation events. In sum, RL13 binds human IgG and may contribute to HCMV immune evasion in the infected host, but this function does not readily explain the instability of the RL13 gene during viral propagation in cultured cells.
authors.affiliation: Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Cortese
authors.forename: Stefano
authors.initials: S
authors.lastname: Calò
authors.forename: Romina
authors.initials: R
authors.lastname: D'Aurizio
authors.forename: Anders
authors.initials: A
authors.lastname: Lilja
authors.forename: Nicola
authors.initials: N
authors.lastname: Pacchiani
authors.forename: Marcello
authors.initials: M
authors.lastname: Merola
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D003587:Cytomegalovirus / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010957:Plasmids; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D016865:Reassortant Viruses / Q000276:immunology / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D014764:Viral Proteins