HOST-CELL DEPENDENCE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 DRUG-RESISTANCE PROFILES AND TISSUE-CULTURE SELECTION PATTERNS

Clinical isolates of the human immunodeficiency virus type 1 (HIV-1) d isplayed differential sensitivity to antiviral nucleosides depending o n the type of host cell employed for viral propagation. Viruses derive d from the peripheral blood mononuclear cells (PBMC) of subjects on pr olonged 3'-azido-3'-deoxythymidine (AZT) therapy behaved as AZT-resist ant when tested in either cord blood mononuclear cells or MT-4 cells b ut as relatively drug-sensitive in the U-937 monocytic cell line. Viru ses 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 mut ations at either position 65 or 184 in the HIV pol gene, were generall y less susceptible to each of 2'-3'-dideoxyinosine (ddl), 2',3'-dideox ycytidine (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 a nd 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.