Relative Activities of HIV-1-III B and HIV-1 BaL LTR and tat in Primary Monocytes and Lymphocytes

Abstract

The mechanisms determining the ability of some but not other strains of human immunodeficiency virus type 1 (HIV-1) to grow in peripheral blood monocyte-macrophages are presently unclear. The tat gene of HIV-1-III_B which replicates poorly in human macrophages, and the tat gene of HIV-1-_BaL, which replicates to high titers in the same cells in transient expression systems with their respective long terminal repeats (LTR) driving a reporter chloramphenicol acetyl transferase (CAT) gene were compared. The authors hypothesized that the tat gene and LTR of BaL might help account for its efficient growth in primary monocyte-macrophages by virtue of a high activity in these cells relative to that of the III_B tat and LTR. Primary peripheral blood lymphocytes and monocytes were cotransfected with either the HIV-1_BaL or HIV-1-III_B LTR fused to the CAT gene and their respective tat genes. The III_B tat and LTR were at least as active in primary lymphocytes as the BaL combination, and both tat-LTR pairs were more active in primary lymphocytes than monocytes. The same relative activities were also observed in primary monocytes after in vitro maturation to macrophages prior to transfection. These data strongly suggest that neither the tat gene nor the LTR of HIV-1-III_B and HIV-1_BaL can account for the great ability of the latter or the inability of the former to grow in monocyte-macrophages.