Characterization and Sequencing of Prototypic Human T-Lymphotropic Virus Type 1 (HTLV-1) from an HTLV-1/2 Seroindeterminate Patient

Abstract

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.

Serological, Epidemiological, and Molecular Differences between Human T-Cell Lymphotropic Virus Type 1 (HTLV-1)-Seropositive Healthy Carriers and Persons with HTLV-I Gag Indeterminate Western Blot Patterns from the Caribbean

“…However, a recent report has described the amplification of an HTLV-1 tax sequence from patients with neurological disease exhibiting an HGIP WB reactivity. This suggests that this seroindeterminate WB pattern might be associated in some rare cases with defective HTLV-1 strains or with a novel retrovirus having homology with HTLV-1, or finally with slowly replicating HTLV-1 (39,47). In addition, it seems unlikely that the HGIP may represent a delayed or slow seroconversion, because most of our followed-up subjects did not show any evolution of their WB profile over time and because the minority who did became EIA negative.…”

Human T‐cell lymphotropic virus types I and II (HTLV‐I and ‐II) infection among seroindeterminate cases in Argentina

“…Several studies have demonstrated that among low-risk BD even from endemic areas for HTLV-I/II infection exhibiting HGIP or Gag (p24) seroindeterminate patterns are unlikely to be infected with HTLV-I/II Busch et al, 2000;Rouet et al, 2001]. The HGIP profile was observed in a HAM/TSP case confirmed as HTLV-I positive by molecular diagnosis [Waziri et al, 2000]. In Martinique, neurological patients with chronic progressive myelopathies, but seronegative for HTLV-I, were further confirmed as HTLV-I positive by n-PCR [d 'Auriol et al, 1990].…”

“…In Martinique, neurological patients with chronic progressive myelopathies, but seronegative for HTLV-I, were further confirmed as HTLV-I positive by n-PCR [d 'Auriol et al, 1990]. Several studies have amplified HTLV-I tax sequences among seroindeterminate Gag samples from patients with neurological diseases or BD suggesting defective HTLV, novel retrovirus, or low proviral load [Waziri et al, 2000;Mangano et al, 2004].…”

A New and Frequent Human T-Cell Leukemia Virus Indeterminate Western Blot Pattern: Epidemiological Determinants and PCR Results in Central African Inhabitants

“…It is also an important issue for comparative analysis between epidemiological studies performed in areas with low and high endemicity, especially in intertropical areas. The significance of these frequent indeterminate WB can be various but, in the majority of the cases, remains mostly unknown and a matter of discussion (24,28,57,69). Indeed, in rare cases, these patterns have been associated with (i) HTLV-1 but mostly HTLV-2 infection exhibiting an atypical HTLV serology (6,34,44,52,68,73,74), (ii) HTLV-1 seroconversion (17,45,46), and (iii) infection by a different HTLV, such as HTLV-3 or HTLV-4 (12,13,42,62,72).…”