Document 0786
 DOCN  M9590786
 TI    Defective accessory genes in a human immunodeficiency virus type
       1-infected long-term survivor lacking recoverable virus.
 DT    9509
 AU    Michael NL; Chang G; d'Arcy LA; Ehrenberg PK; Mariani R; Busch MP; Birx
       DL; Schwartz DH; Division of Retrovirology, Walter Reed Army Institute
       of; Research, Rockville, MD 20850, USA.
 SO    J Virol. 1995 Jul;69(7):4228-36. Unique Identifier : AIDSLINE +
 AB    We have been studying a patient who acquired human immunodeficiency
       virus (HIV) infection via a blood transfusion 13 years ago. She has
       remained asymptomatic since that time. The blood donor and two other
       recipients have all died of AIDS. Although this patient has shown
       persistently strong seroreactivity to HIV type 1 (HIV-1) antigens by
       Western blot (immunoblot), she has been continually HIV culture negative
       in results from multiple laboratories over the last 6 years and has a
       very low viral burden. Her CD4+ T-cell count has fluctuated around a
       mean of 399 cells per microliters, with little change in lymphocyte
       subset percentages. Strong cellular immune responses to HIV-1 epitopes
       by this patient have been demonstrated. We now report the results of an
       intensive molecular genetic analysis of the HIV-1 proviral quasispecies
       from this patient sampled over 5 years. Long terminal repeat region
       sequences supported the argument for normal basal and Tat-mediated
       promoter activities. Sequential sequencing of the nef gene revealed a
       low frequency (8.3%) of defective genes and a striking lack of sequence
       evolution. Functional analysis of predominant nef genes by both a cell
       surface CD4 downregulation and a viral infectivity complementation assay
       showed wild-type function. In contrast, sequential analysis of an
       amplicon containing the vif, vpr, vpu, tat1, and rev1 genes revealed the
       presence of inactivating mutations in 64% of the clones. These data
       suggest that this patient, initially infected with a virulent swarm of
       HIV-1, is presently infected with a more-attenuated viral quasispecies
       as a result of effective host immunity.
 DE    Acquired Immunodeficiency Syndrome/IMMUNOLOGY/*VIROLOGY  Adult  Amino
       Acid Sequence  Base Sequence  CD4 Lymphocyte Count  Female  Genes, nef
       Genes, tat  *Genes, Viral  Human  HIV Long Terminal Repeat
       HIV-1/*GENETICS/ISOLATION & PURIF  Molecular Sequence Data  Mutation
       Support, U.S. Gov't, P.H.S.  Survivors  Trans-Activation (Genetics)
       JOURNAL ARTICLE

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