Identification and expression of human cytomegalovirus transcription units coding for two distinct Fcgamma receptor homologs.
Cellular receptors for the Fc domain of immunoglobulin G (IgG) (FcgammaRs) comprise a family of surface receptors on immune cells connecting humoral and cellular immune responses. Several herpesviruses induce FcgammaR activities in infected cells. Here we identify two distinct human cytomegalovirus (HCMV)-encoded vFcgammaR glycoproteins of 34 and 68 kDa. A panel of HCMV strains exhibited a slight molecular microheterogeneity between Fcgamma-binding proteins, suggesting their viral origin. To locate the responsible genes within the HCMV genome, a large set of targeted HCMV deletion mutants was constructed. The mutant analysis allowed the identification of a spliced UL119-UL118 mRNA to encode vFcgammaR gp68 and TRL11/IRL11 to encode vFcgammaR gp34. Both vFcgammaRs are surface resident type I transmembrane glycoproteins. Significant relatedness of sequences in the extracellular chain of gpUL119-118 and gpTRL11 with particular immunoglobulin supergene family domains present in FcgammaR I and FcgammaRs II/III, respectively, indicates a different ancestry and function of gpUL119-118 and gpTRL11. The HCMV-encoded vFcgammaRs highlight an impressive diversification and redundancy of FcgammaR structures.
Atalay
Ramazan
R
Robert Koch-Institut, Fachgebiet Virale Infektionen, 13353 Berlin, Germany.
Zimmermann
Albert
A
Wagner
Markus
M
Borst
Eva
E
Benz
Christine
C
Messerle
Martin
M
Hengel
Hartmut
H
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000821:virology; D017353:Gene Deletion; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; C464820:UL119-UL118 glycoprotein, Human cytomegalovirus; D014764:Viral Proteins; D000514:alpha 1-Antichymotrypsin; C104832:gp34 protein, cytomegalovirus