Genetic control of infection of primary macrophages with T-cell-tropic strains of HIV-1.
Human immunodeficiency virus type 1 (HIV-1) NDK, a Zairian subtype D virus highly cytopathic for CD4-positive lymphocytes, and the prototype subtype B virus HIV-1 LAV are about 10(4) and 10(5) times more infectious, respectively, for T lymphocytes than for blood-derived macrophages (BDM). Recombinant viruses derived from HIV-1 LAV and HIV-1 NDK were used to determine the genetic control and the step of the virus/cell cycle responsible for infection of BDM with T-cell-tropic viruses. We found that recombinants bearing the envelope glycoprotein of HIV-1 NDK are able to enter more efficiently into BDM than recombinants with HIV-1 LAV envelope glycoprotein. We also found that a genetic region outside of the env gene is responsible for production of HIV-1 NDK infectious progeny from BDM. This region consists of the vif gene and the C- and N-terminal portions of pol and vpr genes, respectively. Our results suggest that productive infection of primary macrophages with T-cell-tropic strains of HIV-1 is determined by two different genetic mechanisms: one effective at the virus/cell entry, controlled by the env gene, and the second after entry, controlled by genes vif and vpr. In comparison with HIV-1 LAV, HIV-1 NDK has been able to more easily overcome both restriction mechanisms.
Hirsch
I
I
Unité de Recherches sur les Rétrovirus et Maladies Associées, INSERM U322, Marseille, France.
de Mareuil
J
J
Salaun
D
D
Chermann
J C
JC
D002460:Cell Line; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000821:virology*; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology
D016655:HIV Core Protein p24