New insights into prevalence, genetic diversity, and proviral load of human T-cell leukemia virus types 1 and 2 in pregnant women in Gabon in equatorial central Africa

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is highly endemic in areas of central Africa; mother-to-child transmission and sexual transmission are considered to be the predominant routes. To determine the prevalence and subtypes of HTLV-1/2 in pregnant women in Gabon, we conducted an epidemiological survey in the five main cities of the country. In 907 samples, the HTLV-1 seroprevalence was 2.1%, which is lower than that previously reported. Only one case of HTLV-2 infection was found. The HTLV-1 seroprevalence increased with age and differed between regions (P </= 0.05), with the highest prevalence (5%) in the southeastern region. A wide range of HTLV-1 proviral loads was observed among the infected women. The level of the proviral load was correlated with a high HTLV-1 antibody titer (P </= 0.02). Sequencing of HTLV-1 env and long terminal repeat fragments showed that all but one strain belonged to the central African subtype B; the outlier was of cosmopolitan subtype A. The new strains of subtype B exhibited wide genetic diversity, but there was no evidence of clustering of specific genomes within geographical regions of the country. Some strains were closely related to simian T-cell leukemia virus type 1 strains of great apes, suggesting that in these areas some HTLV-1 strains could arise from relatively recent interspecies transmission. The sole HTLV-2 strain belonged to subtype B. In this study we showed that the prevalence of HTLV-1 in the southeast is one of the highest in the world for pregnant women.

FIG. 1.

Map of Gabon, with the main cities and “departments” in which the study was conducted.

FIG. 2.

Comparison of HTLV-1 copy numbers in blood of infected pregnant women and HTLV-1 titers as measured by immunofluorescence assay with the HTLV-1-infected MT-2 cell line.

FIG. 3.

Phylogenetic trees for HTLV-1 env and LTR. (A) env phylogenetic tree constructed by the neighbor-joining method on a fragment of 522 bp encoding the end of the carboxyl terminus of the product of the gp46 gene and most of the product of the gp21 gene in 47 HTLV-1 strains, including 16 new strains from pregnant women in Gabon (Gab; in boldface). (B) LTR phylogenetic tree constructed by the neighbor-joining method with 40 HTLV-1 strains, including 18 new strains from pregnant women from Gabon (in boldface) for a portion of 450 bp from the LTR. PTM3 (STLV-1 strain) was used to root the tree. Numbers along ancestral segments indicate the robustness of each node, as estimated by 1,000 bootstrap samplings of the data. The accession numbers of all sequences included in the phylogenetic tree are given in parentheses. For subtype B, sequences from nonhuman primates are indicated by asterisks.

FIG. 4.

Phylogenetic trees for HTLV-2 env and LTR sequences, including the newly isolated strain (Gab1080FC) from central Africa. (A) The phylogenetic tree was constructed with a 537-bp region of HTLV-2 env, including the 19 major strains for HTLV-2 subtypes A and B. The env sequence of the STLV-2 (PP1664) isolate was used as an outgroup to root the tree. (B) Phylogenetic tree of LTR sequences (645 bp), including the new HTLV-2 sequence and 21 published sequences for subtypes A and B. The LTR of the STLV-2 (PP1664) isolate was used as an outgroup to root the tree.