Possible involvement of cell fusion and viral recombination in generation of human immunodeficiency virus variants that display dual resistance to AZT and 3TC.

We have attempted to relate genetic recombination involving human immunodeficiency virus type 1 (HIV-1) to multiple drug resistance by using PEG to fuse subclones of U937 cells that carried HIV-1 recombinants resistant to either 3' -azido-3'-deoxythymidine (AZT) or the (--) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC). The parental viruses employed contained well-defined mutations in the pol gene. Fused cells were co-cultured with the MT4 lymphocyte cell line for virus amplification to yield progeny that, in some cases, possessed different patterns of drug resistance from parental viruses. Mutational analyses were performed by PCR to substantiate these observations, which were also confirmed by direct sequencing of single strands of DNA segments, obtained from plaque-purified viruses. These studies indicate that viral recombination had occurred, and establish a theoretical basis on which to conclude that the acquisition of multiple drug resistance on the part of HIV-1 may be related to its ability to promote cell fusion.