H. Salomon et al., HOST-CELL DEPENDENCE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 DRUG-RESISTANCE PROFILES AND TISSUE-CULTURE SELECTION PATTERNS, Antiviral chemistry & chemotherapy, 6(4), 1995, pp. 222-229
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.