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).