Human immunodeficiency virus and the hematopoietic repertoire: implications for gene therapy.
The human immunodeficiency virus (HIV) infects primarily the hematopoietic and immune systems. At the onset of infection, an initial activation of the immune system occurs, with a subsequent suppression thereafter due to direct viral infection of cells, inhibitory effects of HIV proteins, an altered microenvironment with cytokine imbalance, and increased apoptosis of both infected and non-infected cells. The CD34+ hematopoietic stem cell, however, remains free of infection. Novel methods in gene therapy utilize viral vectors that can introduce genes with good efficiency into the non-dividing stem cell. Therefore, HIV-resistance genes can be introduced into stem cells using these vectors. This confers resistance to infection to their respective progeny, and concurrently allows for repopulation of the immuno-hematopoietic repertoire. Applications of this technology to the patient infected with HIV are discussed in the context of myeloablative therapy and stem cell rescue.
Panoskaltsis
N
N
University of Rochester Medical Center, Hematology/Oncology Unit, 601 Elmwood Ave, Box 610, Rochester, NY 14642, USA.
Abboud
C N
CN
D018952:Antigens, CD34 / Q000276:immunology; D001853:Bone Marrow / Q000502:physiology; D019070:Cell Lineage; D016207:Cytokines / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D006678:HIV / Q000276:immunology* / Q000472:pathogenicity; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000502:physiology / Q000821:virology*; D006706:Homeostasis; D006801:Humans; D017154:Stromal Cells / Q000502:physiology
D018952:Antigens, CD34; D016207:Cytokines