Characterization and sequencing of prototypic human T-lymphotropic virus type 1 (HTLV-1) from an HTLV-1/2 seroindeterminate patient

Serological screening for human T-lymphotropic virus type 1 (HTLV-1) parall els the standard screening process for human immunodeficiency virus (HIV), in which samples found positive by enzyme-linked immunosorbent assay (ELISA ) are confirmed with a modified Western blot procedure. There are a signifi cant number of cases in which HTLV-1/2 ELISA-positive specimens demonstrate an incomplete banding pattern on this Western blot. Individuals providing these atypical antibody responses are categorized as seroindeterminate for HTLV-1/2. Although HTLV-1 genomic sequences are readily detectable in the p eripheral blood lymphocytes (PBL) of seropositive individuals, previous stu dies have repeatedly demonstrated that PBL from the vast majority of HTLV-1 /2 seroindeterminate individuals are PCR negative for HTLV-1, As a result, identification of the agent responsible for this indeterminate reactivity h as been of interest. We have generated an HTLV-1-positive B-cell line (SI-1 B) from one of these seroindeterminate individuals. Previous screening for HTLV-1 in PBL from this patient had been routinely negative by primary PCR ; however, HTLV-1 far had been periodically detected by nested PCR. DNA seq uence data generated with genomic DNA from the SI-1 B cell line and HTLV-1- specific primers demonstrated the presence of a full-length viral genome wi th >97% homology to the Cosmopolitan form of HTLV-1. A 12-bp deletion was i dentified in the 3'-gag/5'-prot region, which would predict translation of altered or nonfunctional proteins from these genes. We propose that this HT LV-1/2-seroindeterminate patient is infected with a prototypic form of HTLV -1 at an extremely low viral load and that this finding may explain HTLV-1/ 2 seroindeterminate reactivity in at least a subset of these individuals.