The effects of β-2-microglobulin on the infectivity of murine cytomegalovirus

Abstract

The role of β-2-microglobulin (β2m) in murine cytomegalovirus (MCMV) infection of susceptible (H-2^d) and resistant (H-2^k) murine embryo fibroblasts (MEF) and peritoneal macrophages was evaluated using serum-free virus (SF-MCMV). The infectivity of SF-MCMV was significantly lower than virus propagated in serum, although the concentrations of virions were similar. Infection of cells with SF-MCMV was assessed by measuring the proportion of cells expressing viral antigens, the sizes of plaques formed in fibroblast monolayers and TCID₅₀ titers. Infection of susceptible fibroblasts was significantly increased 1.6–4.7 fold by the addition of whole FCS, a50 titers by 3.5–10 fold in susceptible MEF. In relatively resistant H-2^k cells, the TCID₅₀ titer and the proportion of cells expressing viral antigens after infection with SF-MCMV were not affected by β2m or FCS, but plaque sizes were increased 2.5–3 fold in resistant BALB.K MEF. When human or murine β2m was added to infected cultures, immunogold electron microscopy revealed these proteins to be always associated extracellularly with the tegument material of disrupted multicapsid virions, but rarely with the envelope of intact virions. However, no murine β2m was found in association with the envelope or tegument of SF-MCMV. These relatively modest effects of β2m which were restricted to genetically susceptible cells, may be due to tegument-bound β2m facilitating infection by capsids, or the stabilisation of the conformation of Class 1 molecules by exogenous β2m, promoting MCMV binding to the target cell.