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) parallels 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 significant 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 peripheral blood lymphocytes (PBL) of seropositive individuals, previous studies 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 has 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 tax had been periodically detected by nested PCR. DNA sequence 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 with >97% homology to the Cosmopolitan form of HTLV-1. A 12-bp deletion was identified in the 3'-gag/5'-prot region, which would predict translation of altered or nonfunctional proteins from these genes. We propose that this HTLV-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.
Waziri
A
A
Viral Immunology Section, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA.
Soldan
S S
SS
Graf
M D
MD
Nagle
J
J
Jacobson
S
S
D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000821:virology; D015139:Blotting, Southern; D015153:Blotting, Western; D002999:Clone Cells; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017353:Gene Deletion; D016356:Gene Products, tax / Q000235:genetics; D016679:Genome, Viral; D015490:HTLV-I Infections / Q000097:blood / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D015367:Human T-lymphotropic virus 2 / Q000276:immunology; D006801:Humans; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D012689:Sequence Homology, Nucleic Acid; D014764:Viral Proteins / Q000235:genetics
D000914:Antibodies, Viral; D017931:DNA Primers; D016356:Gene Products, tax; D012367:RNA, Viral; D014764:Viral Proteins