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Macrophage tropism determinants of human immunodeficiency virus type 1 in vivo
P Westervelt1, D B Trowbridge, L G Epstein
1Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Abstract:
Strains of human immunodeficiency virus type 1 differ in their abilities to infect and replicate in primary human macrophages. Chimeric clones were constructed from a provirus unable to infect macrophages (NLHX) and envelope sequences (V3 loop) of viruses derived without cultivation from brain (YU2 and w1-1c1) or spleen (w2-1b4) tissues. The substituted V3 loop sequences in each case were sufficient to confer upon NLHX the ability to infect macrophages. Furthermore, an envelope domain immediately N terminal to the V3 loop also was found to modulate the level of replication in macrophages. These results demonstrate that an envelope determinant derived directly from patients with AIDS confers HIV-1 tropism for macrophages.
Insights
Human immunodeficiency virus type 1 (HIV-1) envelope sequences, specifically the V3 loop, determine macrophage tropism. This finding reveals key viral determinants for HIV-1 infection in macrophages.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Primary human macrophages are crucial targets for human immunodeficiency virus type 1 (HIV-1) infection.
- Different HIV-1 strains exhibit varying capacities to infect and replicate within these macrophages.
Purpose of the Study:
- To identify the specific viral determinants responsible for HIV-1 tropism in primary human macrophages.
- To investigate the role of envelope gene sequences in conferring macrophage infectivity.
Main Methods:
- Construction of chimeric HIV-1 clones by combining a macrophage-noninfectious provirus (NLHX) with envelope V3 loop sequences from patient-derived viruses.
- Analysis of macrophage infection and replication levels using these chimeric constructs.
Main Results:
- Substitution of the V3 loop sequences from brain or spleen-derived viruses into NLHX conferred the ability to infect macrophages.
- An envelope domain N-terminal to the V3 loop modulated the replication level in macrophages.
Conclusions:
- HIV-1 envelope V3 loop sequences are sufficient to confer macrophage tropism.
- Specific envelope determinants from patients with acquired immunodeficiency syndrome (AIDS) directly influence HIV-1 tropism for macrophages.