K. Toohey et al., HUMAN-IMMUNODEFICIENCY-VIRUS ENVELOPE V1 AND V2 REGIONS INFLUENCE REPLICATION EFFICIENCY IN MACROPHAGES BY AFFECTING VIRUS SPREAD, Virology, 213(1), 1995, pp. 70-79
The vs hypervariable region of the HIV-I envelope protein is a major d
eterminant of viral tropism for macrophages. However, the replication
of macrophage-tropic HIV-1 strains varies considerably in macrophages,
and this variability has been linked to the V1 and V2 envelope region
s. In the present study, recombinant HIV clones were generated by inse
rting V1 and V2 sequences from the Ba-L HIV isolate, which has a high
macrophage replication level, into the genomic background of a macroph
age-tropic clone with a low macrophage replication level. Infection of
macrophages with varying multiplicities of infection and direct detec
tion of the number of infected macrophages per culture showed that the
Ba-L V1 and V2 envelope sequences enhanced the ability of virus to sp
read in the cultures. In contrast, macrophage-tropic clones with low r
eplication efficiency infected macrophages initially but showed no evi
dence of spread to additional cells during the culture period. This ef
fect on virus spread appeared to be macrophage-specific as it was not
observed in cultures of T lymphocytes. Comparison of recombinant clone
s containing V1, V2, and vs envelope sequences from high-efficiency Ba
-L and JR-FL strains indicated that markedly different V1 and V2 seque
nces could impart the same rapidly spreading phenotype in macrophages.
(C) 1995 Academic Press, Inc.