A Novel Human T-lymphotropic Virus Type 1c Molecular Variant in an Indigenous Individual from New Caledonia, Melanesia

Cassar, Olivier; Charavay, Françoise; Touzain, F.; Jeannin, Patricia; Grangeon, Jean-Paul; Laumond, Sylvie; Chungue, Eliane; Martin, Paul; Gessain, Antoine

doi:10.1371/journal.pntd.0005278

Cited by 9 publications

(7 citation statements)

References 20 publications

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“…In contrast, the main difference was seen against the Melanesian/Australian HTLV-1 genotype (1c), which is the most divergent [52,53], and even presents high diversity within the same genotype [54,55]. Therefore, although HTLV-1c prevalence varies greatly in Melanesia, from 0.6% in Ni-Vanuatu and New Caledonia ethnicities [54,56] to 33.6% in indigenous population in Central Australia [7], this genotype is not found elsewhere [6,14,53]. Thus, it would be interesting to have the LAMP assays described here tested among these populations, since this genotype was not present in our cohort [47].…”

Section: Discussionmentioning

confidence: 89%

“…The HTLV-1 tax sequence recognized by LAMP primers had only one nucleotide substitution between the Cosmopolitan Transcontinental (1aA) and Japanese (1aB) genotypes, which are the most prevalent in Brazil and Japan, respectively [6]. In contrast, the main difference was seen against the Melanesian/Australian HTLV-1 genotype (1c), which is the most divergent [52,53], and even presents high diversity within the same genotype [54,55]. Therefore, although HTLV-1c prevalence varies greatly in Melanesia, from 0.6% in Ni-Vanuatu and New Caledonia ethnicities [54,56] to 33.6% in indigenous population in Central Australia [7], this genotype is not found elsewhere [6,14,53].…”

Section: Discussionmentioning

confidence: 99%

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Loop-Mediated Isothermal Amplification (LAMP) Assay for Rapid and Accurate Confirmatory Diagnosis of HTLV-1/2 Infection

Gomes

Caterino–de–Araujo

Campos

et al. 2020

Viruses

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Laboratory diagnosis of human T-lymphotropic viruses (HTLV) 1 and 2 infection is performed by serological screening and further confirmation with serological or molecular assays. Thus, we developed a loop-mediated isothermal nucleic acid amplification (LAMP) assay for the detection of HTLV-1/2 in blood samples. The sensitivity and accuracy of HTLV-1/2 LAMP were defined with DNA samples from individuals infected with HTLV-1 (n = 125), HTLV-2 (n = 19), and coinfected with HIV (n = 82), and compared with real-time polymerase chain reaction (qPCR) and PCR-restriction fragment length polymorphism (RFLP). The overall accuracy of HTLV-1/2 LAMP (95% CI 74.8–85.5%) was slightly superior to qPCR (95% CI 69.5–81.1%) and similar to PCR-RFLP (95% CI 79.5–89.3%). The sensitivity of LAMP was greater for HTLV-1 (95% CI 83.2–93.4%) than for HTLV-2 (95% CI 43.2–70.8%). This was also observed in qPCR and PCR-RFLP, which was associated with the commonly lower HTLV-2 proviral load. All molecular assays tested showed better results with samples from HTLV-1/2 mono-infected individuals compared with HIV-coinfected patients, who present lower CD4 T-cell counts. In conclusion, HTLV-1/2 LAMP had similar to superior performance than PCR-based assays, and therefore may represent an attractive alternative for HTLV-1/2 diagnosis due to reduced working time and costs, and the simple infrastructure needed.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Loop-Mediated Isothermal Amplification (LAMP) Assay for Rapid and Accurate Confirmatory Diagnosis of HTLV-1/2 Infection

Gomes

Caterino–de–Araujo

Campos

et al. 2020

Viruses

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“…Isolates from Australia are indicated in bold. Isolates NCP201, VAN-EM5, and MEL5 were obtained from New Caledonia, Vanuatu [84], and the Solomon Islands [85], respectively. Sequence variations are highlighted in pink.…”

Section: Discussionmentioning

confidence: 99%

“…To gain additional insight into the role of p13 in HTLV-1 pathogenesis, we extended our analysis to the p13 proteins coded by 37 subtype C sequences, 34 of which were isolated from Australian patients (Fig. 5) [82][83][84][85]. Sequence information for 4 amino-terminal amino acids was not available for 8 GenBank entries (prefix KC in Fig.…”

Section: Sequence Variation Of P13mentioning

confidence: 99%

Functional properties and sequence variation of HTLV-1 p13

et al. 2020

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Human T cell leukemia virus type-1 (HTLV-1) was the first retrovirus found to cause cancer in humans, but the mechanisms that drive the development of leukemia and other diseases associated with HTLV-1 infection remain to be fully understood. This review describes the functional properties of p13, an 87-amino acid protein coded by HTLV-1 open reading frame II (orf-II). p13 is mainly localized in the inner membrane of the mitochondria, where it induces potassium (K +) influx and reactive oxygen species (ROS) production, which can trigger either proliferation or apoptosis, depending on the ROS setpoint of the cell. Recent evidence indicates that p13 may influence the cell's innate immune response to viral infection and the infected cell phenotype. Association of the HTLV-1 transcriptional activator, Tax, with p13 increases p13's stability, leads to its partial co-localization with Tax in nuclear speckles, and reduces the ability of Tax to interact with the transcription cofactor CBP/p300. Comparison of p13 sequences isolated from HTLV-1-infected individuals revealed a small number of amino acid variations in the domains controlling the subcellular localization of the protein. Disruptive mutations of p13 were found in samples obtained from asymptomatic patients with low proviral load. p13 sequences of HTLV-1 subtype C isolates from indigenous Australian patients showed a high degree of identity among each other, with all samples containing a pattern of 5 amino acids that distinguished them from other subtypes. Further characterization of p13's functional properties and sequence variants may lead to a deeper understanding of the impact of p13 as a contributor to the clinical manifestations of HTLV-1 infection.

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“…Because p30 functionally affects cell cycle progression, host immune response, and oncogenic transformation, it is possible that the putative HTLV-1C p30 could influence disease outcome. We performed an amino acid comparison analysis of orf-II in both subtypes using the sequences of 160 individuals infected with HTLV-1A (Additional file 1: Figure S1) [77], 22 Australian patients infected with HTLV-1C [137], and previously published HTLV-1C sequences [131][132][133]138]. A consensus was generated among the p30 sequences of the two subtypes (Additional file 2: Figure S2).…”

Section: Htlv-1c Orf IImentioning

confidence: 99%

p30 protein: a critical regulator of HTLV-1 viral latency and host immunity

et al. 2019

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The extraordinarily high prevalence of HTLV-1 subtype C (HTLV-1C) in some isolated indigenous communities in Oceania and the severity of the health conditions associated with the virus impress the great need for basic and translational research to prevent and treat HTLV-1 infection. The genome of the virus's most common subtype, HTLV-1A, encodes structural, enzymatic, and regulatory proteins that contribute to viral persistence and pathogenesis. Among these is the p30 protein encoded by the doubly spliced Tax-orf II mRNA, a nuclear/nucleolar protein with both transcriptional and post-transcriptional activity. The p30 protein inhibits the productive replication cycle via nuclear retention of the mRNA that encodes for both the viral transcriptional trans-activator Tax, and the Rex proteins that regulate the transport of incompletely spliced viral mRNA to the cytoplasm. In myeloid cells, p30 inhibits the PU-1 transcription factor that regulates interferon expression and is a critical mediator of innate and adaptive immunity. Furthermore, p30 alters gene expression, cell cycle progression, and DNA damage responses in T-cells, raising the hypothesis that p30 may directly contribute to T cell transformation. By fine-tuning viral expression while also inhibiting host innate responses, p30 is likely essential for viral infection and persistence. This concept is supported by the finding that macaques, a natural host for the closely genetically related simian T-cell leukemia virus 1 (STLV-1), exposed to an HTLV-1 knockout for p30 expression by a single point mutation do not became infected unless reversion and selection of the wild type HTLV-1 genotype occurs. All together, these data suggest that inhibition of p30 may help to curb and eventually eradicate viral infection by exposing infected cells to an effective host immune response.

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A Novel Human T-lymphotropic Virus Type 1c Molecular Variant in an Indigenous Individual from New Caledonia, Melanesia

Cited by 9 publications

References 20 publications

Loop-Mediated Isothermal Amplification (LAMP) Assay for Rapid and Accurate Confirmatory Diagnosis of HTLV-1/2 Infection

Loop-Mediated Isothermal Amplification (LAMP) Assay for Rapid and Accurate Confirmatory Diagnosis of HTLV-1/2 Infection

Functional properties and sequence variation of HTLV-1 p13

p30 protein: a critical regulator of HTLV-1 viral latency and host immunity

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