       Document 0465
 DOCN  M9620465
 TI    Possible involvement of cell fusion and viral recombination in
       generation of human immunodeficiency virus variants that display dual
       resistance to AZT and 3TC.
 DT    9602
 AU    Gu Z; Gao Q; Faust EA; Wainberg MA; Lady Davis Institute, Jewish General
       Hospital, McGill University,; Montreal, Quebec, Canada.
 SO    J Gen Virol. 1995 Oct;76 ( Pt 10):2601-5. Unique Identifier : AIDSLINE
       MED/96030871
 AB    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.
 DE    Antiviral Agents/*PHARMACOLOGY  Base Sequence  Cell Fusion  Cell Line
       Coculture  Drug Resistance, Multiple/GENETICS  DNA Mutational Analysis
       Genes, pol/GENETICS  Human  HIV-1/*DRUG EFFECTS/GENETICS  Molecular
       Sequence Data  Monocytes  Polymerase Chain Reaction/METHODS
       *Recombination, Genetic  Support, Non-U.S. Gov't  T-Lymphocytes  Virus
       Cultivation  Zalcitabine/*ANALOGS & DERIVATIVES/PHARMACOLOGY
       Zidovudine/*PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

