Document 0789
 DOCN  M9650789
 TI    Detection of human cytomegalovirus mutations associated with ganciclovir
       resistance in cerebrospinal fluid of AIDS patients with central nervous
       system disease.
 DT    9605
 AU    Wolf DG; Lee DJ; Spector SA; Department of Pediatrics, University of
       California, San Diego, La; Jolla 92093-0672, USA.
 SO    Antimicrob Agents Chemother. 1995 Nov;39(11):2552-4. Unique Identifier :
       AIDSLINE MED/96139556
 AB    To examine the involvement of ganciclovir-resistant strains in the
       development of central nervous system (CNS) disease caused by human
       cytomegalovirus (HCMV), 14 AIDS patients with CNS disease caused by HCMV
       were studied for the presence of HCMV strains with UL97 gene mutations
       associated with ganciclovir resistance by using amplification and direct
       sequencing of HCMV DNA in cerebrospinal fluid (CSF). The CSF of all
       seven patients who had not received ganciclovir prior to the development
       of CNS disease and four patients who had been receiving the drug for 3
       to 8 months contained wild-type UL97 sequences. The CSF of three
       patients who had received ganciclovir for 12 to 30 months contained HCMV
       strains with nucleotide changes leading to single-amino-acid
       substitutions within conserved UL97 sites implicated in nucleotide
       binding (position 460) and substrate recognition (position 591).
       Patients containing mutant and wild-type strains revealed a similar
       spectrum of clinical and histopathologic manifestations. These findings
       indicate that CNS disease in AIDS patients receiving prolonged
       ganciclovir therapy can be caused by ganciclovir-resistant HCMV strains.
       Direct genotypic analysis of HCMV DNA within CSF should help to identify
       ganciclovir-resistant virus and to guide anti-HCMV therapy.
 DE    Antiviral Agents/*PHARMACOLOGY/THERAPEUTIC USE  AIDS-Related
       Opportunistic Infections/DRUG THERAPY/*VIROLOGY  Base Sequence  Central
       Nervous System Diseases/DRUG THERAPY/*VIROLOGY  Cytomegalovirus/DRUG
       EFFECTS/*GENETICS  Cytomegalovirus Infections/DRUG THERAPY/*VIROLOGY
       Drug Resistance, Microbial  Ganciclovir/*PHARMACOLOGY/THERAPEUTIC USE
       Genotype  Human  Molecular Sequence Data  Mutation  Polymerase Chain
       Reaction  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

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