Southern African Origin of HTLV-1 in Romania.

In Europe, most HTLV-1-infected individuals originate from highly endemic regions such as West Indies, sub-Saharan Africa, and South America. The only genuine endemic region for HTLV-1 in Europe is Romania where ATL series have been reported among Romanian patients. Our objective is to better understand the origin of this endemic focus based on a study of the genetic diversity of HTLV-1 in Romanians. DNA was obtained from PBMCs/buffy coats of 11 unrelated HTLV-1-infected individuals of Romanian origin. They include 9 ATL cases and 2 asymptomatic carriers. LTR sequences were obtained for all specimens. Complete genomic HTLV-1 sequences were obtained using four PCR series on 10 specimens. Phylogenetic trees were generated from multiple alignments using HTLV-1 prototypic sequences and the new generated sequences. Most of the complete LTR sequences (756-bp) showed low nucleotide diversity, ranging from 0% to 0.8% difference, and were closely related (less than 0.8% divergence) to the only previously characterized Romanian strain, RKI2. One strain, ROU7, diverged slightly (1.5% on average) from the others. Phylogenetic analyses both on partial LTR and the complete genome demonstrate that the 11 sequences belong to the HTLV-1a cosmopolitan genotype and 10 of them belong to the previously denominated a-TC Mozambique-Southern Africa A subgroup. In this study, we demonstrated that the HTLV-1 present in Romania most probably originated in Southern Africa. As most Romanian HTLV-1 strains are very closely related, we can assume that HTLV-1 has been introduced into the Romanian population recently. Further studies are ongoing to decipher the routes of arrival and dissemination of these HTLV-1 strains, and to date the emergence of this endemic focus in Central Europe.

HTLV-2B strains, similar to those found in several Amerindian tribes, are endemic in central African Bakola Pygmies.

BACKGROUND: The presence and origin of endemic foci of human T-lymphotropic virus type 2 (HTLV2) infection in Africa remain a matter of debate. METHODS: To better appreciate such determinants, we performed a survey of 1918 inhabitants from Cameroon forest areas, including 1051 Bakola Pygmies and 867 Bantus. RESULTS: The overall HTLV-1/2 seroprevalence was 4% (49 cases of HTLV-1 and 27 cases of HTLV-2 infection). Both infections were mainly restricted to the Bakola Pygmies, with surprisingly no HTLV-2 infections in the Bantu population. Both HTLV-1 and HTLV-2 seroprevalences increased with age. There was evidence of ongoing HTLV-2 transmission in this population. Lymphoid T cell lines producing HTLV-2 were established. HTLV-2 long terminal repeat sequences (672 base pairs) obtained from 7 infected Bakola were highly similar to each other (<1% nucleotide divergence), as well as to Amerindian HTLV-2B strains. Analyses on a complete sequence (8954 base pairs) confirmed that it was a typical HTLV-2 subtype B strain. Along with molecular clock analysis, these data strongly suggest that HTLV-2 has been endemic in the Bakola Pygmy population for a long time. CONCLUSIONS: This study demonstrates clearly an HTLV-2 endemicity with ongoing transmission in an African population. Furthermore, it give insights into central questions regarding the origins and evolution rate of HTLV-2 and the migrations of infected populations.

Human blood-brain barrier disruption by retroviral-infected lymphocytes: role of myosin light chain kinase in endothelial tight-junction disorganization.

The blood-brain barrier (BBB), which constitutes the interface between blood and cerebral parenchyma, has been shown to be disrupted during retroviral associated neuromyelopathies. Human T cell leukemia virus (HTLV-1)-associated myelopathy/tropical spastic paraparesis is a slowly progressive neurodegenerative disease, in which evidence of BBB breakdown has been demonstrated by the presence of lymphocytic infiltrates in the CNS and plasma protein leakage through cerebral endothelium. Using an in vitro human BBB model, we investigated the cellular and molecular mechanisms involved in endothelial changes induced by HTLV-1-infected lymphocytes. We demonstrate that coculture with infected lymphocytes induces an increase in paracellular endothelial permeability and transcellular migration, via IL-1alpha and TNF-alpha secretion. This disruption is associated with tight junction disorganization between endothelial cells, and alterations in the expression pattern of tight junction proteins such as zonula occludens 1. These changes could be prevented by inhibition of the NF-kappaB pathway or of myosin light chain kinase activity. Such disorganization was confirmed in histological sections of spinal cord from an HTLV-1-associated myelopathy/tropical spastic paraparesis patient. Based on this BBB model, the present data indicate that HTLV-1-infected lymphocytes can induce BBB breakdown and may be responsible for the CNS infiltration that occurs in the early steps of retroviral-associated neuromyelopathies.