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.