Cell cycle arrest during measles virus infection: a G(0)-like block leads to suppression of retinoblastoma protein expression

One of the major mechanisms by which measles virus (MV) infection causes di sease and death is suppression of the immune response. The nonresponsivenes s of MV-infected human lymphocytes to mitogens and a partial block in the G (0)/G(1) phase of the cell cycle observed in vitro is thought to reflect in vivo immunosuppression. In order to molecularly dissect MV-induced immunos uppression, we analyzed expression of surface activation markers and cell c ycle-regulatory proteins in MV-infected human T lymphocytes. MV Edmonston ( MV-Ed) could induce and maintain a high level of the early activation marke r CD69 in the absence of proliferation. Expression of cyclins D3 and E, whi ch positively control entry into S phase, was also significantly decreased. Analysis of inhibitors of progression into S phase showed that a high leve l of p27 was maintained in the G(0)/G(1)-blocked subpopulation of MV-Ed-inf ected cells compared to the proliferating MV-infected cells. Furthermore, c ell cycle-related upregulation of retinoblastoma (Rb) protein synthesis did not occur in the MV-Ed-infected lymphocytes. Acridine orange staining, whi ch distinguishes cells in G(0) from cells in G(1), showed that RNA levels m ere not upregulated following activation, which is consistent with cells re maining in a G(0) state. Although expression of surface activation markers indicated entry into the cycle, intracellular Rb and RNA levels suggested a quiescent state. These results indicate that MV can uncouple activation of T lymphocytes from transition of G(0) to G(1).