Induction of surface IgG receptors in cytomegalovirus‐infected human fibroblasts

Abstract

Binding studies on diploid human fibroblasts with human immunoglobulin G (IgG) demonstrate the existence of a specific receptor for this class of immunoglobulin. The receptor preferentially binds aggregated human IgG and recognizes these complexes via the Fc portion of the molecule. Cytomegalovirus infection of diploid human fibroblasts results in a more than 100-fold increase in the number of IgG-receptors present on the cell surface. We have previously demonstrated that fibroblasts express a receptor with high specificity for human IgG (J. Frey and E. G. Afting unpublished results). It has recently been shown that peripheral tissues, e. g. skin and muscle, account for the highest proportion of IgG catabolism [19]. These tissues contain a high proportion of fibroblasts. The following study was performed in order to investigate IgG receptors on human fibroblasts after virus infection. Here we describe the induction of an Fc-receptor on human fibroblasts following infection with cytomegalovirus (CMV). The induced receptor shows a high affinity for the aggregated Fc domain of human IgG. MATERIALS AND METHODS Cell cultureHuman diploid fibroblasts were obtained from young healthy volunteers by skin biopsy and grown in Dulbecco's minimal essential medium (DMEM, Gibco Wiesbaden, FRG) supplemented with 10% fetal calf serum (Gibco), 2% pyruvate, 2mM glutamine, and non-essential amino acids [20].The cells were maintained at 37 "C in 10 % COz. CMV were propagated in human fibroblasts [21]. For binding studies using infected cells, subconfluent or confluent cells growing in 6 cm petri-dishes were washed twice with serum-free DMEM and subsequently infected with 4 -5 TCIDSO of CMV per cell in 3 ml serum free mcdium for 2 h. After two washing steps the cells were further kept in complete medium. The cell viability was determined by trypan blue exclusion [22].

Identification and Expression of Human Cytomegalovirus Transcription Units Coding for Two Distinct Fcγ Receptor Homologs

“…The GenBank accession number for the UL119-118 nucleotide sequence reported in this article is AY065993. (62), on the cell surface (2,21,43), and in the cytoplasm following infection (22,36) has been reported by a number of laboratories. Both single and multiple biochemical activities associated with different molecular weights have been proposed to mediate Fc-dependent IgG binding, but a specific polypeptide responsible for this effect has not been demonstrated unequivocally.…”

“…Over the last 25 years, several laboratories have reported on Fc binding activities in HCMV-infected cells (21,22,36,58). Biochemical characterization of Fc-binding proteins (FcBPs) in HCMV-infected fibroblasts led to conflicting results, and a viral protein mediating this effect has not yet been identified (48,62,67).…”

Roles of apolipoproteins B and E in the cellular binding of very low density lipoproteins.

“…This effect may be due to a conformational change in the lipoprotein structure induced by antibodybinding to a determinant distant from the cellular recognition site (cooperativity) such that cellular uptake is enhanced. Another explanation of the enhanced uptake is the possible interaction of the antibody-VLDL3 immune complex with a purported Fc receptor on human fibroblast (37). As the Fc receptor binds aggregated IgG or immune complexes preferentially over monomeric IgG, this may explain the increased stimulation of VLDL3 uptake at higher antibody/antigen ratios (Figs.…”

Characterization of IgG Fc Receptors Induced by Human Cytomegalovirus

“…The IgG FcRs on these cells have been well characterized (Hibbs et al, 1986;Lewis et al, 1986). IgG FcRs can also be induced in cells infected with human herpesviruses such as herpes simplex virus type 1 (HSV-1) (Watkins, 1964;Westmoreland & Watkins, 1974), HSV-2 (Para et al, 1982) and human cytomegalovirus (HCMV) (Frey & Einsfelder, 1984;Furukawa et al, 1975;Keller et al, 1976;Rahman et al, 1976;Westmoreland et al, 1976). The FcR induced by HSV has been identified as the 65K to 85K Mr viral glycoprotein E (gE) (Para et al, 1980).…”