Effect of different human immunodeficiency virus type‐1 (HIV‐1) isolates on long‐term bone marrow haemopoiesis

Abstract

Summary. Haemopoietic cytopenias are a frequent occurrence in human immunodeficiency virus type‐1 (HIV‐1) induced disease. In order to examine the possible direct inhibition of marrow haemopoiesis by HIV‐1, we have investigated the effect of HIV‐1 infection on myelopoiesis in long‐term bone marrow cultures. In vitro exposure of normal marrow cultures to three different lymphocytotropic HIV‐1 isolates resulted in productive infection, as demonstrated by a progressive increase of gag p24 antigen. In these experiments, ICR‐3 isolate, but not LAV' or NL4–3 isolates, accelerated the loss of non‐adherent cells. A differential ability of these HIV‐1 isolates to suppress myelopoiesis was confirmed in long‐term cultures in which virus was added continuously. In these cultures, ICR‐3, and to a lesser extent also NL4–3, but not LAV', induced a progressive decrease in the number of total non‐adherent cells as well as non‐adherent colony forming units‐granulocyte/macrophage (CFU‐GM). Furthermore, exposure of normal purified CD34+ cells to ICR‐3 induced defects in their ability to form haemopoietic colonies: this inhibitory effect was significantly relieved by pretreatment of ICR‐3 with an anti‐gp 120 antibody. Similar exposure of CD34+ cells to LAV' and NL4–3 induced no such defects. These data indicate that some HIV‐1 isolates can impair bone marrow haemopoiesis in a dose‐dependent fashion, acting, at least in part, at the level of haemopoietic stem/ progenitor cells.

Myelomonocytic Cell Lines in Modeling HIV-1 Infection of the Bone Marrow

“…Most studies indicate that bone marrow-derived HSCs cannot be infected by HIV-1 until they undergo modest differentiation in order to express the appropriate receptors to enable virus entry and subsequent replication [59]. Studies have demonstrated the presence of both CD4 [94] and the chemokine receptors CXCR4 and CCR5 [95] on CD34 [62,81]. The natural chemokine ligands for the major HIV-1 coreceptors are able to readily block entry of HIV-1 [96].…”

“…HIV-1-infected patients suffer from many hematologic disorders and exhibit uni or multilineage suppression of bone marrow hematopoiesis including anemia, lymphocytopenia, thrombocytopenia, granulocytopenia, monocytopenia, and neutropenia that can be attributed to malfunction or premature death of the specific hematopoietic cells [8, [57][58][59]. The hematopoietic disorders are frequently associated with impaired HPC growth, BM dysplasia, plasmacytosis, and lymphoid infiltrates [57,60], and they suggest virusinduced abnormalities in the bone marrow microenvironment [61][62][63]. T cell depletion in AIDS is thought to be, at least in part, due to the failure of T cell development from lymphohematopoietic stem cells [14].…”