Host Cell Dependence of Human Immunodeficiency Virus Type-1 Drug Resistance Profiles and Tissue Culture Selection Patterns

Abstract

Clinical isolates of the human immunodeficiency virus type 1 (HIV-1) displayed differential sensitivity to antiviral nucleosides depending on the type of host cell employed for viral propagation. Viruses derived from the peripheral blood mononuclear cells (PBMC) of subjects on prolonged 3′-azido-3′-deoxythymidine (AZT) therapy behaved as AZT-resistant when tested in either cord blood mononuclear cells or MT-4 cells but as relatively drug-sensitive in the U-937 monocytic cell line. Viruses derived from monocytes/ macrophages of the same individuals behaved as drug-sensitive in all cells tested. It was also shown that cloned recombinant viruses, which contained defined resistance-conferring mutations at either position 65 or 184 in the HIV pol gene, were generally less susceptible to each of 2′-3′-dideoxyinosine (ddl), 2′,3′-dideoxycytidine (ddC) and the (-)enantiomer of 2′,3′-dideoxy-3′thiacytidine (3TC) in MT-4 cells than in any of PBMC, cord blood mononuclear cells (CBMC) or Jurkat cells. Finally, resistance against each of AZT, ddl and ddC could be selected for more easily using MT-4 cells than CBMC or Jurkat lymphocytes and not at all with the U-937 monocytic cell line.