Human parvovirus B19 infection causes cell cycle arrest of human erythroid progenitors at late S phase that favors viral DNA replication

摘要: Human parvovirus B19 (B19V) infection has a unique tropism to human erythroid progenitor cells (EPCs) in bone marrow and the fetal liver. It been reported that both B19V expression of large nonstructural protein NS1 arrested EPCs at cell cycle status with 4 N DNA content, which was previously claimed be "G2/M arrest." However, mutant infectious (M20(mTAD2)) replicated well B19V-semipermissive UT7/Epo-S1 but did not induce G2/M arrest (S. Lou, Y. Luo, F. Cheng, Q. Huang, W. Shen, S. Kleiboeker, J. Tisdale, Z. Liu, Qiu, Virol. 86:10748-10758, 2012). To further characterize during EPCs, we analyzed change using 5-bromo-2'-deoxyuridine (BrdU) pulse-labeling DAPI (4',6-diamidino-2-phenylindole) staining, precisely establishes pattern based on cellular replication nuclear content. We found although transduction immediately B19V-infected still incorporated BrdU, indicating active synthesis. Notably, BrdU incorporation caused neither by viral nor repair could initiated infection-induced damage. Moreover, several S phase regulators were abundantly expressed colocalized within centers. More importantly, wild-type DNA, as M20(mTAD2) mutant, phase. Taken together, our results confirmed triggers late arrest, presumably provides factors for replication.