VIRAL VARIABILITY AND SERUM ANTIBODY-RESPONSE IN A LABORATORY WORKER INFECTED WITH HIV TYPE-1 (HTLV TYPE IIIB)

Molecular clones of HIV-1 were obtained from isolates cultured from pe ripheral blood mononuclear cells (PBMCs) and directly from uncultured PBMCs from a laboratory worker accidentally infected with the HIV-1 la boratory strain, HIV-1(HTLV-IIIB). Envelope sequences corresponding to the first 752 amino acids of HIV-1(HTLV-IIIB) clone BH10 were obtaine d from clones of cultured virus and sequenced. Three env clones obtain ed shortly after infection differed among themselves at only seven nuc leotide positions, resulting in one amino acid substitution and one fr ameshift mutation. These envelope sequences were as similar to the env elope sequences of various IIIB clones as the latter were to each othe r. env divergence increased over the course of infection. However, the overall diversity in env clones obtained two or more years after infe ction was still comparable to that among IIIB env clones from the orig inal IIIB culture. Multiple clones of partial env gene sequences conta ining the V3 loop were also obtained directly from uncultured PBMCs by polymerase chain reaction amplification. The env sequences of these c lones 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 divergenc e 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 mu tation predominated in all subsequent isolates. Antibodies against the V3 loops of IIIB and divergent 1987 and 1990 LW isolates appeared sim ultaneously in laboratory worker serum and persisted with no significa nt differences in titer. Furthermore, neutralization studies with auto logous sequential sera suggested selection for the A-to-T change in V3 was not due to V3-directed antibodies. These results demonstrate a su rprising homogeneity among env sequences of HIV-1 from an infected lab oratory worker, perhaps because the initial infection originated from a relatively homogeneous population of tissue culture-adapted virus.