Viral Determinants of Cellular Tropism

Cells of mononuclear phagocyte lineage are the predominant cell type producing human immunodeficiency virus type 1 (HIV-1) in extravascular tissues; HIV-1 infection of mononuclear phagocytes may be directly related to primary disease manifestations and also appears to contribute to the immune deficiency of AIDS. Whereas peripheral blood lymphocytes are permissive for nearly all strains of HIV-1, only some HIV-1 strains replicate efficiently in mononuclear phagocytes. Recombinant virus strains have been used to identify a 157-amino acid region of gp120 that can confer macrophage tropism. This region is distinct from the principal CD4 binding domain of gp 120 and includes the major type-specific neutralizing epitope located in the third hypervariable domain, V3. Quantitative assay of HIV-1-specific DNA by polymerase chain reaction early after infection suggests that HIV-1 strain differences in macrophage tropism are determined at the level of entry. These studies suggest that target cell interactions with gpl20 in addition to or in conjunction with the CD4 binding domain are necessary for efficient entry into mononuclear phagocytes.