HIV-1 Determinants of Thrombocytopenia at the Stage of CD34+ Progenitor Cell Differentiation in Vivo Lie in the Viral Envelope Gp120 V3 Loop Region

Overview

Journal Virology

Specialty Microbiology

Date 2010 Mar 27

PMID 20338611

Citations 4

Authors

Menghua Zhang

Stella Evans

Jinyun Yuan

Lee Ratner

Prasad S Koka

Affiliations

Soon will be listed here.

Abstract

HIV-1 V3 loop clones of virus isolates derived from patients suffering from thrombocytopenia were used for infection of the human thymus/liver conjoint hematopoietic organ that developed in the severe combined immunodeficient mouse (SCID-hu Thy/Liv). The V3 loop clones showed a significantly greater degree of inhibition of megakaryopoiesis than myelopoiesis and erythropoiesis of the human CD34+ progenitor cells, in vivo. Inhibition of megakaryopoiesis occurs through reduction in c-Mpl expression and consequent decrease in STAT5 activation. Therefore HIV-1 V3 loop sequences of thrombocytopenic patients exhibit preferential inhibition of megakaryocyte lineage-specific differentiation of CD34+ progenitor cells, thus reflecting the patients' clinical condition.

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References

Voulgaropoulou F, Tan B, Soares M, Hahn B, Ratner L . Distinct human immunodeficiency virus strains in the bone marrow are associated with the development of thrombocytopenia. J Virol. 1999; 73(4):3497-504. PMC: 104119. DOI: 10.1128/JVI.73.4.3497-3504.1999. View

Voulgaropoulou F, Pontow S, Ratner L . Productive infection of CD34+-cell-derived megakaryocytes by X4 and R5 HIV-1 isolates. Virology. 2000; 269(1):78-85. DOI: 10.1006/viro.2000.0193. View

Cole J, Marzec U, Gunthel C, Karpatkin S, Worford L, Sundell I . Ineffective platelet production in thrombocytopenic human immunodeficiency virus-infected patients. Blood. 1998; 91(9):3239-46. View

Jensen M, Coetzer M, van t Wout A, Morris L, Mullins J . A reliable phenotype predictor for human immunodeficiency virus type 1 subtype C based on envelope V3 sequences. J Virol. 2006; 80(10):4698-704. PMC: 1472078. DOI: 10.1128/JVI.80.10.4698-4704.2006. View

Kirito K, Kaushansky K . Transcriptional regulation of megakaryopoiesis: thrombopoietin signaling and nuclear factors. Curr Opin Hematol. 2006; 13(3):151-6. DOI: 10.1097/01.moh.0000219660.03657.4b. View

Chavda S, Griffin P, Keys B, Vekony M, Cann A . Molecular determinants of the V3 loop of human immunodeficiency virus type 1 glycoprotein gp120 responsible for controlling cell tropism. J Gen Virol. 1994; 75 ( Pt 11):3249-53. DOI: 10.1099/0022-1317-75-11-3249. View

Zauli G, Catani L, Gibellini D, Re M, Vianelli N, Colangeli V . Impaired survival of bone marrow GPIIb/IIa+ megakaryocytic cells as an additional pathogenetic mechanism of HIV-1-related thrombocytopenia. Br J Haematol. 1996; 92(3):711-7. DOI: 10.1046/j.1365-2141.1996.367904.x. View

Moliterno A, Williams D, Gutierrez-Alamillo L, Salvatori R, Ingersoll R, Spivak J . Mpl Baltimore: a thrombopoietin receptor polymorphism associated with thrombocytosis. Proc Natl Acad Sci U S A. 2004; 101(31):11444-7. PMC: 509220. DOI: 10.1073/pnas.0404241101. View

Espanol I, Muniz-Diaz E, Margall N, Rabella N, Sambeat M, Hernandez A . Serum thrombopoietin levels in thrombocytopenic and non-thrombocytopenic patients with human immunodeficiency virus (HIV-1) infection. Eur J Haematol. 1999; 63(4):245-50. DOI: 10.1111/j.1600-0609.1999.tb01885.x. View

10.

Koka P, Reddy S . Cytopenias in HIV infection: mechanisms and alleviation of hematopoietic inhibition. Curr HIV Res. 2004; 2(3):275-82. DOI: 10.2174/1570162043351282. View

11.

Utley J . Pathophysiology of cardiopulmonary bypass: current issues. J Card Surg. 1990; 5(3):177-89. DOI: 10.1111/j.1540-8191.1990.tb01036.x. View

12.

Koka P, Fraser J, Bryson Y, Bristol G, Aldrovandi G, Daar E . Human immunodeficiency virus inhibits multilineage hematopoiesis in vivo. J Virol. 1998; 72(6):5121-7. PMC: 110080. DOI: 10.1128/JVI.72.6.5121-5127.1998. View

13.

Mir N, Costello C, Luckit J, Lindley R . HIV-disease and bone marrow changes: a study of 60 cases. Eur J Haematol. 1989; 42(4):339-43. DOI: 10.1111/j.1600-0609.1989.tb01222.x. View

14.

Li J, Xia Y, Kuter D . The platelet thrombopoietin receptor number and function are markedly decreased in patients with essential thrombocythaemia. Br J Haematol. 2000; 111(3):943-53. View

15.

Ratner L . Human immunodeficiency virus-associated autoimmune thrombocytopenic purpura: a review. Am J Med. 1989; 86(2):194-8. DOI: 10.1016/0002-9343(89)90268-4. View

16.

Lathey J, Brambilla D, Goodenow M, Nokta M, Rasheed S, Siwak E . Co-receptor usage was more predictive than NSI/SI phenotype for HIV replication in macrophages: is NSI/SI phenotyping sufficient?. J Leukoc Biol. 2000; 68(3):324-30. View

17.

Goodenow M, Collman R . HIV-1 coreceptor preference is distinct from target cell tropism: a dual-parameter nomenclature to define viral phenotypes. J Leukoc Biol. 2006; 80(5):965-72. DOI: 10.1189/jlb.0306148. View

18.

Koka P, Kitchen C, Reddy S . Targeting c-Mpl for revival of human immunodeficiency virus type 1-induced hematopoietic inhibition when CD34+ progenitor cells are re-engrafted into a fresh stromal microenvironment in vivo. J Virol. 2004; 78(20):11385-92. PMC: 521839. DOI: 10.1128/JVI.78.20.11385-11392.2004. View

19.

Zauli G, Re M, Gugliotta L, Visani G, Vianelli N, Furlini G . Lack of compensatory megakaryocytopoiesis in HIV-1-seropositive thrombocytopenic individuals compared with immune thrombocytopenic purpura patients. AIDS. 1991; 5(11):1345-50. DOI: 10.1097/00002030-199111000-00010. View

20.

Jensen M, Li F, van t Wout A, Nickle D, Shriner D, He H . Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env V3 loop sequences. J Virol. 2003; 77(24):13376-88. PMC: 296044. DOI: 10.1128/jvi.77.24.13376-13388.2003. View