TY - JOUR
T1 - CD4 receptor-dependent entry of human immunodeficiency virus type-1 env-pseudotypes into CCR5-, CCR3-, and CXCR4-expressing human alveolar macrophages is preferentially mediated by the CCR5 coreceptor
AU - Park, In Woo
AU - Koziel, Henry
AU - Hatch, William
AU - Li, Xiuhong
AU - Du, Bin
AU - Groopman, Jerome E.
PY - 1999
Y1 - 1999
N2 - Alveolar macrophages (AM) are important host-defense cells and targets of human immunodeficiency virus type 1 (HIV-1) infection. However, the receptors mediating HIV-1 entry into AM are not completely characterised. We observed that, in addition to CD4 receptors, AM from healthy adults expressed low levels of CCR5, CCR3, and CXCR4 chemokine receptors by flow cytometry, and specific messenger RNA was detected for all three receptors by reverse transcriptase/polymerase chain reaction. The macrophage monocytotropic (M-tropic; YU2) and dual-tropic (89.6) HIV-1 env-pseudotypes entered AM efficiently, as expected given CCR3 and CCR5 expression. However, the T-lymphocytotropic (T-tropic; HXB2) pseudotype did not enter AM despite expression of the appropriate chemokine coreceptor CXCR4. Incubation of AM with regulated on activation, normal T cells expressed and secreted (RANTES) significantly impaired entry of the M-tropic (YU2) HIV-1 pseudotype, whereas SDF-1β or eotaxin did not impair entry. The entry of simian immunodeficiency virus (SIV) pbjl.9 env-pseudotype into AM was not blocked by RANTES, SDF-1β, or eotaxin. The competence of these chemokine receptors for virus entry was confirmed in Cf2Th canine thymocytes cotransfected with the human CD4 and chemokine 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 by CXCR4, and the dual-tropic (89.6) HIV-1 or the SIVpbjl.9 pseudotype by CCR5, CCR3, or CXCR4. Our data indicate that the mechanisms for HIV-1 entry are both receptor-specific and cell type-specific, and that chemokine receptor expression on AM does not fully explain cell susceptibility to different virus isolates.
AB - Alveolar macrophages (AM) are important host-defense cells and targets of human immunodeficiency virus type 1 (HIV-1) infection. However, the receptors mediating HIV-1 entry into AM are not completely characterised. We observed that, in addition to CD4 receptors, AM from healthy adults expressed low levels of CCR5, CCR3, and CXCR4 chemokine receptors by flow cytometry, and specific messenger RNA was detected for all three receptors by reverse transcriptase/polymerase chain reaction. The macrophage monocytotropic (M-tropic; YU2) and dual-tropic (89.6) HIV-1 env-pseudotypes entered AM efficiently, as expected given CCR3 and CCR5 expression. However, the T-lymphocytotropic (T-tropic; HXB2) pseudotype did not enter AM despite expression of the appropriate chemokine coreceptor CXCR4. Incubation of AM with regulated on activation, normal T cells expressed and secreted (RANTES) significantly impaired entry of the M-tropic (YU2) HIV-1 pseudotype, whereas SDF-1β or eotaxin did not impair entry. The entry of simian immunodeficiency virus (SIV) pbjl.9 env-pseudotype into AM was not blocked by RANTES, SDF-1β, or eotaxin. The competence of these chemokine receptors for virus entry was confirmed in Cf2Th canine thymocytes cotransfected with the human CD4 and chemokine 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 by CXCR4, and the dual-tropic (89.6) HIV-1 or the SIVpbjl.9 pseudotype by CCR5, CCR3, or CXCR4. Our data indicate that the mechanisms for HIV-1 entry are both receptor-specific and cell type-specific, and that chemokine receptor expression on AM does not fully explain cell susceptibility to different virus isolates.
UR - http://www.scopus.com/inward/record.url?scp=0033129374&partnerID=8YFLogxK
U2 - 10.1165/ajrcmb.20.5.3547
DO - 10.1165/ajrcmb.20.5.3547
M3 - Article
C2 - 10226056
AN - SCOPUS:0033129374
SN - 1044-1549
VL - 20
SP - 864
EP - 871
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
IS - 5
ER -