TY - JOUR
T1 - Human Immunodeficiency Virus Envelope V1 and V2 Regions Influence Replication Efficiency in Macrophages by Affecting Virus Spread
AU - Toohey, Kathy
AU - Wehrly, Kathy
AU - Nishio, Jane
AU - Perryman, Sylvia
AU - Chesebro, Bruce
PY - 1995/10/20
Y1 - 1995/10/20
N2 - The V3 hypervariable region of the HIV-1 envelope protein is a major determinant of viral tropism for macrophages. However, the replication of macrophage-tropic HIV-1 strins varies considerably in macrophages, and this variability has been linked to the V1 and V2 envelope regions. In the present study, recombinant HIV clones were generated by inserting V1 and V2 sequences from the Ba-L HIV isolate, which has a high macrophage replication level, into the genomic background of a macrophage-tropic clone with a low macrophage replication level. Infection of macrophages with varying multiplicities of infection and direct detection of the number of infected macrophages per culture showed that the Ba-L V1 and V2 envelope sequences enhanced the ability of virus to spread in the cultures. In contrast, macrophage-tropic clones with low replication efficiency infected macrophages initially but showed no evidence of spread to additional cells during the culture period. This effect on virus spread appeared to be macrophage-specific as it was not observed in cultures of T lymphocytes. Comparison of recombinant clones containing V1, V2, and V3 envelope sequences from high-efficiency Ba-L and JR-FL strains indicated that markedly different V1 and V2 sequences could impart the same rapidly spreading phenotype in macrophages.
AB - The V3 hypervariable region of the HIV-1 envelope protein is a major determinant of viral tropism for macrophages. However, the replication of macrophage-tropic HIV-1 strins varies considerably in macrophages, and this variability has been linked to the V1 and V2 envelope regions. In the present study, recombinant HIV clones were generated by inserting V1 and V2 sequences from the Ba-L HIV isolate, which has a high macrophage replication level, into the genomic background of a macrophage-tropic clone with a low macrophage replication level. Infection of macrophages with varying multiplicities of infection and direct detection of the number of infected macrophages per culture showed that the Ba-L V1 and V2 envelope sequences enhanced the ability of virus to spread in the cultures. In contrast, macrophage-tropic clones with low replication efficiency infected macrophages initially but showed no evidence of spread to additional cells during the culture period. This effect on virus spread appeared to be macrophage-specific as it was not observed in cultures of T lymphocytes. Comparison of recombinant clones containing V1, V2, and V3 envelope sequences from high-efficiency Ba-L and JR-FL strains indicated that markedly different V1 and V2 sequences could impart the same rapidly spreading phenotype in macrophages.
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U2 - 10.1006/viro.1995.1547
DO - 10.1006/viro.1995.1547
M3 - Article
C2 - 7483281
AN - SCOPUS:0028866919
VL - 213
SP - 70
EP - 79
JO - Virology
JF - Virology
SN - 0042-6822
IS - 1
M1 - 71547
ER -