CD4 receptor-dependent entry of human immunodeficiency virus type-1 env-pseudotypes into CCR5-, CCR3-, and CXCP4-Expressing human alveolar macrophages is preferentially mediated by the CCR5 coreceptor

Alveolar macrophages (AM) are important host-defense cells and targets of h uman immunodeficiency virus type 1 (HIV-1) infection. However, the receptor s mediating HIV-1 entry into AM are not completely characterized. We observ ed that, in addition to CD4 receptors, AM from healthy adults expressed low levels of CCR5, CCR3, and CXCR4 chemokine receptors by Row cytometry, and specific messenger RNA was detected for all three receptors by reverse tran scriptase/polymerase chain reaction. The macrophage monocytotropic (M-tropi c; YU2) and dual-tropic (89.6) HIV-1 env-pseudotypes entered AM efficiently , as expected given CCR3 and CCR5 expression. However, the T-lymphocytotrop ic (T-tropic; HXB2) pseudotype did not enter AM despite expression of the a ppropriate chemokine coreceptor CXCR4. Incubation of AM with regulated on a ctivation, normal T cells expressed and secreted (RANTES) significantly imp aired entry of the M-tropic (YU2) HIV-1 pseudotype, whereas SDF-1 beta or e otaxin did not impair entry. The entry of simian immunodeficiency virus (SI V) pbj1.9 env-pseudotype into AM was not blocked by RANTES, SDF-1 beta, or eotaxin. The competence of these chemokine receptors for virus entry was co nfirmed in Cf2Th canine thymocytes cotransfected with the human CD4 and che mokine receptors, Entry of the M-tropic (YU2) HIV-1 pseudotype was shown to be mediated by either CCR3 or CCR5, the T-tropic (HXB2) HIV-1 pseudotype b y CXCR4, and the dual-tropic (89.6) HIV-1 or the SIVpbj1.9 pseudotype by CC R5, CCR3, or CXCR4. Our data indicate that the mechanisms for HIV-1 entry a re both receptor-specific and cell type-specific, and that chemokine recept or expression on AM does not fully explain cell susceptibility to different virus isolates.