Patients　with　human　immunodeficiency　virus-1　(HIV-1)　infection　often　present　with　hematopoietic　failure.　As　the　important　hematopoietic　support　cells　in　the　bone　marrow　(BM),　the　BM　mesenchymal　stem　cells　(BMSCs)　can　be　impacted　by　HIV　proteins　that　are　released　by　infected　cells　within　BM.　In　this　study,　we　tested　whether　HIV　protein　p55-gag　could　induce　senescence　of　BMSCs　and　reduce　their　capacity　to　support　expansion　of　hematopoietic　stem　cells　in　vitro.　BMSCs　were　chronically　treated　with　p55-gag　(BMSCgag)　for　up　to　20　days,　and　their　proliferative　activity　and　senescence　makers　were　compared　to　nontreated　cells　(BMSCcon).　Then,　we　analyzed　the　hematopoietic　support　function　of　BMSCcon　and　BMSCgag　by　determining　cellular　proliferation,　colony-forming　ability,　and　primitive　hematopoietic　populations　of　hematopoietic　progenitors　grown　on　the　BMSCs.　In　addition,　we　compared　the　gene　expression　patterns　for　supporting　hematopoiesis　of　BMSCcon　and　BMSCgag.　The　results　show　that　when　compared　to　BMSCcon,　BMSCgag　reduced　their　proliferative　activity　and　underwent　senescence.　The　ability　of　BMSCgag　to　support　the　expansion　of　committed　hematopoietic　progenitors　from　umbilical　cord　blood-derived　CD34(+)cells　may　be　impaired,　while　the　expression　of　genes　associated　with　maintaining　and　enhancing　hematopoiesis　appeared　to　be　decreased　in　treated　BMSCs　compared　to　control　BMSCs.　In　conclusion,　senescence　induced　by　p55-gag　resulted　in　decreased　hematopoietic　support　function　of　BMSCs　through　reducing　a　series　of　hematopoietic　cytokine　expression.