Fm. Kim et al., V3-INDEPENDENT DETERMINANTS OF MACROPHAGE TROPISM IN A PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATE, Journal of virology, 69(3), 1995, pp. 1755-1761
Human immunodeficiency virus type 1 isolates differ in their ability t
o productively infect macrophages, and several groups have mapped the
genetic basis for macrophage tropism to regions of env that include th
e third hypervariable region (V3 loop). We recently described a primar
y isolate (89.6) which is highly macrophage tropic and yet differs fro
m other macrophage-tropic strains studied in that it is cytopathic in
T cells. Genetic mapping of macrophage tropism determinants in this vi
rus was done by using chimeras generated with the prototypic non-macro
phage-tropic strain HXB2. Replacement of a 2.7-kb env containing regio
n of HXB with corresponding sequences from 89.6 conferred the macropha
ge-tropic phenotype, but insertion of the 89.6 V3 loop along with V4/V
5 sequences did not. Conversely, placement of HXB sequences that inclu
ded V3 into 89.6 did not impair this strain's ability to replicate in
macrophages. Sequence analysis of V3 shows that 89.6 differs markedly
from previously described macrophage-tropic consensus sequences and th
at it is more similar to highly charged non-macrophage-tropic strains.
This suggests either that macrophage tropism is defined by structural
determinants resulting from complex interactions among multiple env r
egions rather than V3 sequence-specific requirements or that there are
multiple mechanisms by which different strains may establish producti
ve macrophage infection. In addition, because the HXB V3 loop supports
productive macrophage infection in the background of 89.6, phenotypic
characterization of V3 sequences should be considered specific to the
viral context in which they are placed.