MULTIPLE DETERMINANTS FOR GROWTH OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN MONOCYTE-MACROPHAGES

Attempts to define the genetic determinants required for efficient gro wth of human immunodeficiency virus type 1 (HIV-1) in monocyte-macroph ages were made by constructing chimeras between two infectious clones of HIV-1 (HXB2 and LW/C), which despite only minor differences in thei r DNA sequence have striking differences in cell tropism. Although bot h of them replicate efficiently in peripheral blood mononuclear cells, HXB2 replicates extensively in permanent T cell lines but poorly in p rimary monocyte macrophages (T cell line tropic); the reverse is true for LW/C (macrophage tropic). The envelope proved to contain the major determinants of macrophage tropism. However, tropism determinants app eared to be scattered along the envelope. In particular, the Vs loop a lone appeared to be neither necessary nor sufficient for growth in mac rophages. Both vpr and nef genes appeared to play a less significant r ole to improve viral replication in macrophages, but only in the prese nce of the proper envelope sequences. HIV-1 macrophage tropism thus ap pears to result from the contribution of several different determinant s.