Replication of a macrophage-tropic strain of human immunodeficiency virus type 1 (HIV-1) in a hybrid cell line, CEMx174, suggests that cellular accessory molecules are required for HIV-1 entry.
To investigate the mechanism underlying one aspect of the cellular tropism of human immunodeficiency virus type 1 (HIV-1), we used a macrophage-tropic isolate, 89.6, and screened its ability to infect a number of continuous cell lines. HIV-1 (89.6) was able to replicate robustly in a T-cell/B-cell hybrid line, CEMx174, while it replicated modestly or not at all in either of its parents, one of which is the CD4-positive line CEM.3. Analysis by transfection of a molecular clone, a virus uptake assay, and polymerase chain reaction all provided strong evidence that the block to HIV-1(89.6) replication in the CEM.3 line lies at the level of cellular entry. These results were complemented by preparing a CD4-expressing derivative of the B-cell parent, 721.174, and demonstrating that it is permissive for productive HIV-1(89.6) replication. Given these experimental findings, we speculate that there exist cellular accessory factors which facilitate virus entry and infection in CD4-positive cells. Furthermore, these cellular accessory factors may be quite virus strain specific, since not all macrophage-tropic strains of HIV-1 were able to replicate in the CEMx174 hybrid cell line. This experimental model provides a system for the identification of one or more of these putative cellular accessory factors.
Stefano
K A
KA
Department of Neurology, University of Pennsylvania Medical Center, Philadelphia 19104.
Collman
R
R
Kolson
D
D
Hoxie
J
J
Nathanson
N
N
Gonzalez-Scarano
F
F
D001402:B-Lymphocytes / Q000382:microbiology; D001483:Base Sequence; D015704:CD4 Antigens / Q000502:physiology*; D002460:Cell Line; D015658:HIV Infections / Q000382:microbiology / Q000473:pathology*; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D006822:Hybrid Cells; D066298:In Vitro Techniques; D008264:Macrophages / Q000382:microbiology*; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000502:physiology; D013601:T-Lymphocytes / Q000382:microbiology; D014779:Virus Replication
D015704:CD4 Antigens; D011991:Receptors, Virus