Molecular epidemiology of endemic human T-lymphotropic virus type 1 in a rural community in Guinea-Bissau

Abstract

Background: Human T-Lymphotropic Virus Type 1 (HTLV-1) infection causes lethal adult T-cell leukemia (ATL) and severely debilitating HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in up to 5% of infected adults. HTLV-1 is endemic in parts of Africa and the highest prevalence in West Africa (5%) has been reported in Caio, a rural area in the North-West of Guinea-Bissau. It is not known which HTLV-1 variants are present in this community. Sequence data can provide insights in the molecular epidemiology and help to understand the origin and spread of HTLV-1.

Objective: To gain insight into the molecular diversity of HTLV-1 in West Africa.

Methods: HTLV-1 infected individuals were identified in community surveys between 1990-2007. The complete Long Terminal Repeat (LTR) and p24 coding region of HTLV-1 was sequenced from infected subjects. Socio-demographic data were obtained from community census and from interviews performed by fieldworkers. Phylogenetic analyses were performed to characterize the relationship between the Caio HTLV-1 and HTLV-1 from other parts of the world.

Results: LTR and p24 sequences were obtained from 72 individuals (36 LTR, 24 p24 only and 12 both). Consistent with the low evolutionary change of HTLV-1, many of the sequences from unrelated individuals showed 100% nucleotide identity. Most (45 of 46) of the LTR sequences clustered with the Cosmopolitan HTLV-1 subtype 1a, subgroup D (1aD). LTR and p24 sequences from two subjects were divergent and formed a significant cluster with HTLV-1 subtype 1g, and with the most divergent African Simian T-cell Lymphotropic Virus, Tan90.

Conclusions: The Cosmopolitan HTLV-1 1aD predominates in this rural West African community. However, HTLV-1 subtype 1g is also present. This subtype has not been described before in West Africa and may be more widespread than previously thought. These data are in line with the hypothesis that multiple monkey-to-man zoonotic events are contributing to HTLV-1 diversity.

Figure 1. ML tree of 630-bp LTR sequences from 48 Caio infected subjects (Caio sequences in red).

Also included are 66 STLV/HTLV-1 reference sequences (in black); Mel5 was used as an outgroup. The names of the countries of origin are denoted in brackets (CAR, Central African Republic). The phylogenetic tree was inferred under a Tamura-Nei evolutionary model with a gamma model of among-site substitution rate heterogeneity. Bootstrap values using 1000 replicates of ≥60 are indicated on the branches. The asterisks indicate significant branch length on ML testing (* p-value≤0.001; ** p-value≤0.05). The scale bar represents the number of nucleotide substitutions per site. The scale of the MarB43 is not on scale because it did not fit in the figure. Sequences identical to Caio4676 are Caio4126, Caio4142, Caio4315, Caio4768, Caio5324, Caio5801, Caio6460, Caio6936 and Caio7120. Sequence identical to Caio4647 is Caio4650. Sequence identical to Caio4799 is Caio4801. Sequences identical to Caio5620 are Caio4743, Caio4745 and Caio5883. Sequences identical to Caio5187 are Caio5846, Caio5884 and Caio5931. Sequences identical to Caio4634 are Caio4635 and Caio5448. Sequences identical to Caio4758 are: Caio4658, Caio4659 and Caio4757. Sequence identical to Caio4671 is Caio4702. Sequences identical to 7580 are 7421 and 7661. Only one example of each set of identical sequences was included in the analysis.

Figure 2. ML tree of 647-bp p24 sequences from 36 Caio infected subjects (Caio sequences in red).

Also included are 15 STLV/HTLV-1 reference sequences (in black); Mel5 was used as an outgroup. The countries of origin are denoted in brackets (CAR, Central African Republic; NA, not available). The phylogenetic tree was inferred under a Tamura-Nei evolutionary model with a gamma model of among-site substitution rate heterogeneity. Bootstrap values using 1000 replicates of ≥60 are indicated on the branches. The asterisks indicate significant branch length on ML testing (* p-value≤0.001; ** p-value≤0.05). The scale bar represents the number of nucleotide substitutions per site. Sequences identical to Caio4009 are Caio4072, Caio4106, Caio4112, Caio4211, Caio4315, Caio4328, Caio4358, Caio4383, Caio4417, Caio4418, Caio5801, Caio6473, Caio6590, Caio65396 and Caio65407. Sequence identical to Caio65363 is Caio65571. Sequence identical to Caio4258 is Caio65325. Only one example of each set of identical sequences was included in the analysis.