title: Cell cycle arrest during measles virus infection: a G0-like block leads to suppression of retinoblastoma protein expression.
abstract: One of the major mechanisms by which measles virus (MV) infection causes disease and death is suppression of the immune response. The nonresponsiveness of MV-infected human lymphocytes to mitogens and a partial block in the G0/G1 phase of the cell cycle observed in vitro is thought to reflect in vivo immunosuppression. In order to molecularly dissect MV-induced immunosuppression, we analyzed expression of surface activation markers and cell cycle-regulatory proteins in MV-infected human T lymphocytes. MV Edmonston (MV-Ed) could induce and maintain a high level of the early activation marker CD69 in the absence of proliferation. Expression of cyclins D3 and E, which positively control entry into S phase, was also significantly decreased. Analysis of inhibitors of progression into S phase showed that a high level of p27 was maintained in the G0/G1-blocked subpopulation of MV-Ed-infected cells compared to the proliferating MV-infected cells. Furthermore, cell cycle-related upregulation of retinoblastoma (Rb) protein synthesis did not occur in the MV-Ed-infected lymphocytes. Acridine orange staining, which distinguishes cells in G0 from cells in G1, showed that RNA levels were not upregulated following activation, which is consistent with cells remaining in a G0 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 G0 to G1.
authors.affiliation: Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA. naniche@scripps.edu
authors.forename: D
authors.initials: D
authors.lastname: Naniche
authors.forename: S I
authors.initials: SI
authors.lastname: Reed
authors.forename: M B
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D056743:Cyclin D3; D016213:Cyclins / Q000032:analysis; D016193:G1 Phase; D006801:Humans; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008457:Measles / Q000276:immunology* / Q000378:metabolism; D008840:Microfilament Proteins / Q000032:analysis; D009124:Muscle Proteins; D012335:RNA, Ribosomal / Q000096:biosynthesis; D016192:Resting Phase, Cell Cycle; D016160:Retinoblastoma Protein / Q000096:biosynthesis*; D000099192:CD69 Antigens