       Document 1013
 DOCN  M9541013
 TI    Viral variability and serum antibody response in a laboratory worker
       infected with HIV type 1 (HTLV type IIIB).
 DT    9504
 AU    Reitz MS Jr; Hall L; Robert-Guroff M; Lautenberger J; Hahn BM; Shaw GM;
       Kong LI; Weiss SH; Waters D; Gallo RC; et al; Laboratory of Tumor Cell
       Biology, National Cancer Institute,; National Institutes of Health,
       Bethesda, Maryland 20892.
 SO    AIDS Res Hum Retroviruses. 1994 Sep;10(9):1143-55. Unique Identifier :
       AIDSLINE MED/95127297
 AB    Molecular clones of HIV-1 were obtained from isolates cultured from
       peripheral blood mononuclear cells (PBMCs) and directly from uncultured
       PBMCs from a laboratory worker accidentally infected with the HIV-1
       laboratory strain, HIV-1(HTLV-IIIB). Envelope sequences corresponding to
       the first 752 amino acids of HIV-1(HTLV-IIIB) clone BH10 were obtained
       from clones of cultured virus and sequenced. Three env clones obtained
       shortly after infection differed among themselves at only seven
       nucleotide positions, resulting in one amino acid substitution and one
       frameshift mutation. These envelope sequences were as similar to the
       envelope sequences of various IIIB clones as the latter were to each
       other. env divergence increased over the course of infection. However,
       the overall diversity in env clones obtained two or more years after
       infection was still comparable to that among IIIB env clones from the
       original IIIB culture. Multiple clones of partial env gene sequences
       containing the V3 loop were also obtained directly from uncultured PBMCs
       by polymerase chain reaction amplification. The env sequences of these
       clones were generally similar to those of the cultured viruses. Within
       the V3 region, the earliest isolates retained the sequence of the HXB2
       clone from IIIB. Clones obtained later showed a progressive divergence
       in V3. An A-to-T substitution within the GPGRAF sequence at the tip of
       the V3 loop was observed within 1 year after infection, and this
       mutation predominated in all subsequent isolates. Antibodies against the
       V3 loops of IIIB and divergent 1987 and 1990 LW isolates appeared
       simultaneously in laboratory worker serum and persisted with no
       significant differences in titer. Furthermore, neutralization studies
       with autologous sequential sera suggested selection for the A-to-T
       change in V3 was not due to V3-directed antibodies. These results
       demonstrate a surprising homogeneity among env sequences of HIV-1 from
       an infected laboratory worker, perhaps because the initial infection
       originated from a relatively homogeneous population of tissue
       culture-adapted virus.
 DE    Acquired Immunodeficiency Syndrome/BLOOD/IMMUNOLOGY/*VIROLOGY  Amino
       Acid Sequence  Antibody Formation  Base Sequence  Cells, Cultured
       Comparative Study  DNA Primers  Frameshift Mutation  Gene Products,
       env/CHEMISTRY/GENETICS  *Genes, env  Human  HIV-1/*GENETICS/*ISOLATION &
       PURIF/PHYSIOLOGY  *Laboratory Personnel
       Lymphocytes/IMMUNOLOGY/*VIROLOGY  Molecular Sequence Data  Occupational
       Diseases/BLOOD/IMMUNOLOGY/*VIROLOGY  Phylogeny  Polymerase Chain
       Reaction  Support, Non-U.S. Gov't  Support, U.S. Gov't, Non-P.H.S.
       Support, U.S. Gov't, P.H.S.  Time Factors  Variation (Genetics)  Virus
       Replication  JOURNAL ARTICLE

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

