scholarly journals HIV-1LAI Nef blocks the development of hematopoietic stem/progenitor cells into myeloid-erythroid lineage cells

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wei Zou ◽  
Juanjuan Xing ◽  
Shijie Zou ◽  
Mei Jiang ◽  
Xinping Chen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Progenitor Cells ◽  
Cell Loss ◽  
Underlying Mechanism ◽  
Humanized Mice ◽  
Hematopoietic Stem ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Abstract Background A variety of hematopoietic abnormalities are commonly seen in human immunodeficiency virus-1 (HIV-1) infected individuals despite antiviral therapy, but the underlying mechanism remains elusive. Nef plays an important role in HIV-1 induced T cell loss and disease progression, but it is not known whether Nef participates in other hematopoietic abnormalities associated with infection. Results In the current study we investigated the influence of HIV-1LAI Nef (LAI Nef) on the development of hematopoietic stem/progenitor cells (HSPCs) into myeloid-erythroid lineage cells, and found that nef expression in HSPCs blocked their differentiation both in vitro and in humanized mice reconstituted with nef-expressing HSPCs. Conclusions Our novel findings demonstrate LAI Nef compromised the development of myeloid-erythroid lineage cells, and therapeutics targeting Nef would be promising in correcting HIV-1 associated hematopoietic abnormalities.

scholarly journals Use of RetroNectin in studies requiring in vitro HIV-1 infection of human hematopoietic stem/progenitor cells

2017 ◽  
Author(s):  
Tetsuo Tsukamoto ◽  
Seiji Okada
Keyword(s):  
Human Immunodeficiency Virus ◽  
Gene Transfer ◽  
Detailed Analysis ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Hematopoietic System ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Hiv 1

AbstractHuman immunodeficiency virus (HIV) causes damage, directly or indirectly, to the whole hematopoietic system including CD34+hematopoietic stem/progenitor cells (HSPC). CXCR4-tropic strains of HIV-1 may be potent to affect the function of CD34+CXCR4+progenitor cells either by infecting the cells or by modifying the dynamics of more differentiated hematopoietic cells. However, CD34+cells are known for the resistance to HIV-1 infection in vitro, restricting the detailed analysis of the impact of HIV upon HSPC. Here the authors report a use of RetroNectin, a recombinant fibronectin fragment used for gene transfer with lentiviral vectors, to overcome the limitation.

scholarly journals Impaired in vitro growth of purified (CD34+) hematopoietic progenitors in human immunodeficiency virus-1 seropositive thrombocytopenic individuals

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2680-2687 ◽  
Author(s):  
G Zauli ◽  
MC Re ◽  
B Davis ◽  
L Sen ◽  
G Visani ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Liquid Culture ◽  
Cell Number ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Immunodeficiency Virus ◽  
P24 Antigen ◽  
Hiv 1

Abstract In this report the role played by human immunodeficiency virus type-1 (HIV-1) in the pathogenesis of HIV-1-related thrombocytopenia was investigated. CD34+ hematopoietic stem/progenitor cells were purified from the bone marrow (BM) of HIV-1(+) thrombocytopenic patients, HIV- 1(+) nonthrombocytopenic individuals, HIV-1(-) patients with immune thrombocytopenic purpura, and HIV-1(-) normal donors. CD34+ cells from HIV-1(+) thrombocytopenic individuals alone showed a reduced capacity to give rise to megakaryocytic colonies (CFU-Meg) and also a progressive and significant decline in cell number when placed in liquid culture containing recombinant human interleukin-3 (rIL-3). This decline involved not only megakaryocyte but also erythroid and granulocyte/macrophage progenitors. The defects in megakaryocyte colony formation and CD34+ cell growth did not result from a productive HIV-1 infection of CD34+ cells. Moreover, HIV-1 DNA was absent from CD34+ cells in 10 of 12 thrombocytopenic patients examined. On the other hand, the decreased survival/proliferation of CD34+ cells in liquid culture, within the HIV-1(+) thrombocytopenic patients, was correlated with the presence of HIV-1 p24 antigen in BM plasma. These results demonstrate an impairment of CD34+ cells in HIV-1(+) individuals presenting thrombocytopenia as the only hematologic manifestation. Furthermore, these findings suggest that increased viral replication in the BM microenvironment may cause this impairment and possibly contributes to HIV-induced thrombocytopenia.

scholarly journals Human Immunodeficiency Virus-1 Infection Interrupts Thymopoiesis and Multilineage Hematopoiesis In Vivo

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2672-2678 ◽  
Author(s):  
Morgan Jenkins ◽  
Mary Beth Hanley ◽  
Mary Beth Moreno ◽  
Eric Wieder ◽  
Joseph M. McCune
Keyword(s):  
Human Immunodeficiency Virus ◽  
Progenitor Cells ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Progenitor ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

It is still uncertain whether multilineage hematopoietic progenitor cells are affected by human immunodeficiency virus-1 (HIV-1) infection in vivo. The SCID-hu Thy/Liv model is permissive of long-term multilineage human hematopoiesis, including T lymphopoiesis. This model was used to investigate the effects of HIV-1 infection on early hematopoietic progenitor function. We found that both lineage-restricted and multilineage hematopoietic progenitors were depleted from grafts infected with either a molecular clone or a primary isolate of HIV-1. Depletion of hematopoietic progenitors (including CD34+ cells, colony-forming units in methylcellulose, and long-term culture-initiating cells) occurred several days before the onset of thymocyte depletion, indicating that the subsequent rapid decline in thymocyte numbers was due at least in part to loss of thymocyte progenitors. HIV-1 proviral genomes were not detected at high frequency in hematopoietic cells earlier than the intrathymic T-progenitor cell stage, despite the depletion of such cells in infected grafts. Proviral genomes were also not detected in colonies derived from progenitor cells from infected grafts. These data demonstrate that HIV-1 infection interrupts both lineage-restricted and multilineage hematopoiesis in vivo and suggest that depletion of early hematopoietic progenitor cells occurs in the absence of direct viral infection.

Human CD34+ Cells Express CXCR4 and Its Ligand Stromal Cell–Derived Factor-1. Implications for Infection by T-Cell Tropic Human Immunodeficiency Virus

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 62-73 ◽  
Author(s):  
Alessandro Aiuti ◽  
Lucia Turchetto ◽  
Manuela Cota ◽  
Arcadi Cipponi ◽  
Andrea Brambilla ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Progenitor Cells ◽  
Stromal Cell ◽  
Human Cd34 ◽  
Cd34 Cells ◽  
Immunodeficiency Virus ◽  
Stromal Cell Derived Factor ◽  
Hiv 1

Human CD34+ hematopoietic progenitor cells obtained from bone marrow (BM), umbilical cord blood (UCB), and mobilized peripheral blood (MPB) were purified and investigated for the expression of the chemokine receptor CXCR4 and its ligand, stromal cell–derived factor-1 (SDF-1). CXCR4 was found present on the cell surface of all CD34+ cells, although it was expressed at lower density on MPB with respect to BM CD34+ cells. Freshly isolated and in vitro–cultured CD34+ cells also coexpressed SDF-1 mRNA, as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Of interest, CD34+/CD38+ committed progenitor cells, unlike primitive CD34+/CD38− cells, expressed SDF-1 mRNA. Supernatants from in vitro–cultured CD34+ cells contained substantial (3 to 8 ng/mL) amounts of SDF-1 by enzyme-linked immunosorbent assay and induced migration of CD34+ cells. Because CD34+ cells express low levels of CD4, the primary receptor of the human immunodeficiency virus (HIV), and CXCR4 is a coreceptor for T-cell tropic (X4) HIV strains, we investigated the susceptibility of CD34+cells to infection by this subset of viruses. Lack of productive infection was almost invariably observed as determined by a conventional RT activity in culture supernatants and by real-time PCR for HIV DNA in CD34+ cells exposed to both laboratory adapted (LAI) and primary (BON) X4 T-cell tropic HIV-1 strain. Soluble gp120 Env (sgp120) from X4 HIV-1 efficiently blocked binding of the anti-CD4 Leu3a monoclonal antibody (MoAb) to either human CD4+ T cells or CD34+ cells. In contrast, sgp120 interfered with an anti-CXCR4 MoAb binding to human T lymphocytes, but not to CD34+ cells. However, CXCR4 on CD34+ cells was downregulated by SDF-1. These results suggest that CXCR4 and its ligand SDF-1 expressed in CD34+ progenitors may play an important role in regulating the local and systemic trafficking of these cells. Moreover, these findings suggest multiple and potentially synergistic mechanisms at the basis of the resistance of CD34+ cells to X4 HIV infection, including their ability to produce SDF-1, and the lack of CXCR4 internalization following gp120 binding to CD4.

Induction of Human Immunodeficiency Virus 1 Replication by Human Herpesvirus 8

2001 ◽  
Vol 125 (6) ◽  
pp. 785-789 ◽  
Author(s):  
Maria Mercader ◽  
Brian J. Nickoloff ◽  
Kimberly E. Foreman
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
B Cell ◽  
Human Herpesvirus ◽  
Human Herpesvirus 8 ◽  
Herpesvirus 8 ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Abstract Background.—Human immunodeficiency virus 1 (HIV-1)–infected individuals are commonly infected with herpesviruses, including cytomegalovirus, herpes simplex virus, varicella-zoster virus, and human herpesvirus 8 (HHV-8, also known as Kaposi sarcoma–associated herpesvirus [KSHV]). Previous studies have demonstrated that coinfection with herpesviruses can modulate HIV-1 replication. This can occur either through direct interaction between the 2 viruses or through secondary effects resulting from the release of cellular factors in response to infection. Objective.—To investigate HIV-1 replication in the presence and absence of HHV-8. Design and Methods.—HIV-1 replication was analyzed following culture of HIV-1–infected CD4+ T cells in the presence of HHV-8 infected B-cell lines or control, uninfected B-cell lines. To confirm and extend the results of these in vitro studies, HIV-1–infected T cells were injected into human skin transplanted onto severe combined immunodeficient mice. The human skin was also injected with purified HHV-8 or phosphate-buffered saline as a control and HIV replication measured in biopsy specimens taken 5 to 8 days later. Results and Conclusions.—The results demonstrated a significant increase in HIV-1 replication in the presence of HHV-8 in both the in vitro and in vivo model systems. Although the mechanism responsible for HHV-8 induction of HIV-1 replication remains to be identified, the results indicate that these 2 viruses may interact at the molecular level in coinfected patients, resulting in increased HIV-1 viral load.

Lack of evidence for infection of or effect on growth of hematopoietic progenitor cells after in vivo or in vitro exposure to human immunodeficiency virus

Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2476-2482 ◽  
Author(s):  
JM Molina ◽  
DT Scadden ◽  
M Sakaguchi ◽  
B Fuller ◽  
A Woon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Human Immunodeficiency Virus ◽  
Progenitor Cells ◽  
Bone Marrow Cells ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Marrow Cells

The pathogenesis of the hematologic abnormalities commonly observed in patients with acquired immunodeficiency syndrome (AIDS) is incompletely understood. We report here that in vitro growth of myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells from six patients with AIDS was not significantly different from that of normal human immunodeficiency virus (HIV) seronegative donors: 25.3 +/- 5 CFU-GM per 5 x 10(4) low density marrow cells and 33.5 +/- 5 BFU-E were observed in AIDS patients versus 32.7 +/- 5 CFU-GM and 42.1 +/- 5 BFU-E in controls. Furthermore, no HIV-DNA in individual colonies (CFU-GM and BFU-E) could be detected using the polymerase chain reaction (PCR) technique, although HIV-1 DNA was detected in peripheral blood mononuclear cells from the same patients. Similarly, normal bone marrow cells exposed in vitro to different isolates of HIV or recombinant purified HIV-1 envelope glycoprotein (gp) 120 did not exhibit any difference in growth of CFU-GM or BFU-E as compared with mock exposed bone marrow cells. HIV- 1 DNA could not be detected by the PCR technique in individual colonies derived from HIV exposed marrow. This study suggests that committed myeloid and erythroid progenitors from AIDS patients are responsive to hematopoietic growth factors in vitro and do not appear to contain HIV- 1 DNA. Also, HIV or its envelope gp did not alter the growth of hematopoietic progenitor cells in vitro. No evidence of HIV infection of progenitor cells could be demonstrated. Impaired hematopoiesis in patients with AIDS may not be related to direct effects of HIV on committed progenitor cells.

scholarly journals Inhibition of productive human immunodeficiency virus-1 infection by cobalamins

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1281-1287 ◽  
Author(s):  
JB Weinberg ◽  
DL Sauls ◽  
MA Misukonis ◽  
DC Shugars
Keyword(s):  
Human Immunodeficiency Virus ◽  
Blood Monocytes ◽  
Inhibitory Effects ◽  
Immunodeficiency Virus ◽  
Normal Human ◽  
Enzyme Cofactors ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Various cobalamins act as important enzyme cofactors and modulate cellular function. We investigated cobalamins for their abilities to modify productive human immunodeficiency virus-1 (HIV-1) infection of hematopoietic cells in vitro. We show that hydroxocobalamin (OH-Cbl), methylcobalamin (Me-Cbl), and adenosylcobalamin Ado-Cbl (Ado-Cbl) inhibit HIV-1 infection of normal human blood monocytes and lymphocytes. The inhibitory effects were noted when analyzing the monocytotropic strains HIV-1-BaL and HIV-1-ADA as well as the lymphocytotropic strain HIV-1-LAI. Cobalamins did not modify binding of gp120 to CD4 or block early steps in viral life cycle, inhibit reverse transcriptase, inhibit induction of HIV-1 expression from cells with established or latent infection, or modify monocyte interferon-alpha production. Because of the ability to achieve high blood and tissue levels of cobalamins in vivo and the general lack of toxicity, cobalamins should be considered as potentially useful agents for the treatment of HIV-1 infection.

scholarly journals Infection of Human Marrow Stroma by Human Immunodeficiency Virus-1 (HIV-1) Is Both Required and Sufficient for HIV-1–Induced Hematopoietic Suppression In Vitro: Demonstration by Gene Modification of Primary Human Stroma

Blood ◽  
1997 ◽  
Vol 90 (5) ◽  
pp. 1787-1798 ◽  
Author(s):  
Ingrid Bahner ◽  
Karen Kearns ◽  
Sunita Coutinho ◽  
Earl H. Leonard ◽  
Donald B. Kohn
Keyword(s):  
Human Immunodeficiency Virus ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Cellular Proliferation ◽  
Cell Layer ◽  
Immunodeficiency Virus ◽  
Cell Layers ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

Abstract Patients with human immunodeficiency virus-1 (HIV-1) infection often present with bone marrow (BM) failure that may affect all hematopoietic lineages. It is presently unclear whether this failure reflects a direct viral impairment of the CD34+ hematopoietic progenitor cells or whether the virus affects the BM microenvironment. To study the effects of HIV-1 on the BM microenvironment, we examined the stromal cell monolayers in long-term BM culture (LTBMC), which are the in vitro equivalent of the hematopoietic microenvironment. We assessed the hematopoietic support function (HSF ) of human stromal layers by determining the cellular proliferation and colony-forming ability of hematopoietic progenitors from BM cells grown on the stromal layers. We show that the HSF is reduced by in vitro infection of the human stromal cell layer by a monocytotropic isolate of HIV-1 (JR-FL). There is no loss of HSF when the stromal cell layer is resistant to HIV-1 replication, either using murine stromal cell layers that are innately resistant to HIV-1 infection or using human stromal cells genetically modified to express a gene that inhibits HIV-1 replication (an RRE decoy). Decreased HSF was seen using either human or murine hematopoietic cells, if the stromal cells were human cells that were susceptible to HIV-1 infection. These in vitro studies implicate HIV-1 replication in the stroma as the essential component causing decreased hematopoietic cell production in HIV-1 infection.

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