Intrahost variations in the envelope receptor-binding domain (RBD) of HTLV-1 and STLV-1 primary isolates

Abstract

Four primate (PTLV), human (HTLV) and simian (STLV) T-cell leukemia virus types, have been characterized thus far, with evidence of a simian zoonotic origin for HTLV-1, HTLV-2 and HTLV-3 in Africa. The PTLV envelope glycoprotein surface component (SUgp46) comprises a receptorbinding domain (RBD) that alternates hypervariable and highly conserved sequences. To further delineate highly conserved motifs in PTLV RBDs, we investigated the intrahost variability of HTLV-1 and STLV-1 by generating and sequencing libraries of DNA fragments amplified within the RBD of the SUgp46 env gene. Using new and highly cross-reactive env primer pairs, we observed the presence of Env quasispecies in HTLV-1 infected individuals and STLV-1 naturally infected macaques, irrespective of the clinical status. These intrahost variants helped us to define highly conserved residues and motifs in the RBD. The new highly sensitive env PCR described here appears suitable for the screening of all known variants of the different PTLV types and should, therefore, be useful for the analysis of seroindeterminate samples.

Searching for Common Mammalian Retroviruses in Pediatric Idiopathic Diseases

“…Efficient detection was achieved with nested PCR, or semi-nested PCR in the case of PTLV detection, while specificity was ensured by selecting an arrangement of consensus motifs within the Env RBD variable domains. We previously described the effectiveness of this method by detecting new HTLV-1/STLV-1 variants [ 19 ] or HTLV-2/4 variants (unpublished results). While we are confident that the pediatric disease samples we tested did not contain retroviruses that harbor the targeted env sequences, we cannot formally eliminate the potential presence of infectious retroviruses that would harbor widely divergent env .…”

“…These sets of primers distinguished BLV, FeLV, PERV, GaLV, MMTV, or MPMV while encompassing all members of each class ( Table 1 ). This strategy, with which we have identified new HTLV and STLV variants [ 19 ], maintained the potential to isolate new retroviruses or variants that are likely to share those highly conserved short motifs.…”

“…PCR was performed based on a sensitive semi-nested assay initially developed to detect all known HTLV and STLV types (1–4) [ 19 ]. Anchoring PCR on conserved motifs within the RBD, which is the most variable region of env , thus selectively enhanced detection of exogenous infections.…”

No evidence for XMRV association in pediatric idiopathic diseases in France

“…The SpA samples were previously tested for the presence of HTLV-related sequences using a sensitive semi-nested DNA amplification method allowing the detection of all PTLV-like sequences [24]. No HTLV-like sequences were found in SpA patients (unpublished data).…”

Conservation of a Neutralization Epitope of Human T-cell Leukemia Virus Type 1 (HTLV-1) among Currently Endemic Clinical Isolates in Okinawa, Japan

“…Although the mutation rate of HTLV-1 is fourfold lower than that of HIV-1, the reverse transcriptase of HTLV-1 also has mutagenicity [35]. Indeed, it has been shown that the receptor binding region of HTLV-1 env localized outside of the LAT-27 epitope shows intra-host variability within HTLV-1-infected individuals [36]. Thus, as the LAT-27 neutralization epitope is well conserved across HTLV-1 subtypes, this region could represent a crucial target of passive immunization.…”