scholarly journals Candidate Polyanionic Microbicides Inhibit Human T-Cell Lymphotropic Virus Type 1 Receptor Interactions, Cell-Free Infection, and Cell-Cell Spread

2008 ◽  
Vol 53 (2) ◽  
pp. 678-687 ◽  
Author(s):  
Daniela Romer ◽  
David W. Brighty ◽  
Cynthia L. Robson ◽  
Quentin J. Sattentau

ABSTRACT The human T-cell lymphotropic virus type 1 (HTLV-1) is the cause of adult T-cell leukemia and inflammatory diseases including HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 can be transmitted through sexual contact, mother-to-child transmission, and exposure to contaminated blood. Microbicides are agents that interfere with microbial infectivity at mucous membranes, and candidates are under development for use against sexually transmitted viruses such as human immunodeficiency virus type 1. We previously demonstrated that cell surface polyanionic heparan sulfate proteoglycans bind the HTLV-1 envelope glycoprotein surface subunit gp46, facilitating cell-cell and cell-free virus spread in vitro. We now show, using assays for Env-receptor binding inhibition, Env-induced cell-cell fusion, cell-cell virus spread, and pseudotype HTLV-1 infectivity, that the soluble polyanions PRO 2000 and dextran sulfate are potent inhibitors of HTLV-1 spread in vitro, with PRO 2000 being the more promising candidate. The results of these studies suggest that candidate topical microbicides may be of use in reducing HTLV-1 sexual transmission.

2017 ◽  
Vol 372 (1732) ◽  
pp. 20160272 ◽  
Author(s):  
Charles R. M. Bangham ◽  
Masao Matsuoka

Human T-cell leukaemia virus type 1 (HTLV-1) causes not only adult T-cell leukaemia-lymphoma (ATL), but also inflammatory diseases including HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 transmits primarily through cell-to-cell contact, and generates abundant infected cells in the host in order to survive and transmit to a new host. The resulting high proviral load is closely associated with the development of ATL and inflammatory diseases. To increase the number of infected cells, HTLV-1 changes the immunophenotype of infected cells, induces proliferation and inhibits apoptosis through the cooperative actions of two viral genes, tax and HTLV-1 bZIP factor ( HBZ ). As a result, infected cells survive, proliferate and infiltrate into the tissues, which is critical for transmission of the virus. Thus, the strategy of this virus is indivisibly linked with its pathogenesis, providing a clue for prevention and treatment of HTLV-1-induced diseases. This article is part of the themed issue ‘Human oncogenic viruses’.


Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1598-1606 ◽  
Author(s):  
T de Revel ◽  
A Mabondzo ◽  
G Gras ◽  
B Delord ◽  
P Roques ◽  
...  

Abstract The tropism of the human T-cell leukemia virus type 1 (HTLV-1) for the cells of monocyte-macrophage lineage was evaluated by the coculture of blood monocyte-derived macrophages, with irradiated cells of HTLV-1 producing cell lines MT2 or C91/PL. The susceptibility to HTLV-1 was assessed by the detection of viral DNA using the polymerase chain reaction method. HTLV-1 gene expression in the cells was detected using in situ hybridization and by immunofluorescent staining of viral antigen. The presence of type C virus-like particles detected by electron microscopy and the ability to infect normal cord blood lymphocytes demonstrated that the infected macrophages produced infectious virus. These results indicate that human macrophages are susceptible in vitro to productive HTLV-1 infection, and thus might be involved in the pathogenesis of HTLV-1-related diseases.


2015 ◽  
Vol 2 (2) ◽  
Author(s):  
David Sibon ◽  
Olivier Cassar ◽  
Isabelle Duga ◽  
Chantal Brouzes ◽  
David Ghez ◽  
...  

Abstract Adult T-cell leukemia/lymphoma (ATLL), a T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1), develops in the majority of cases in individuals who were infected with HTLV-1 as young children, by their mother during prolonged breastfeeding. We report the case of a Caucasian French man, whose parents were HTLV-1-seronegative and who developed ATLL after HTLV-1 sexual transmission by a Cameroonian woman. This hypothesis was corroborated by genotyping of the patient's virus, which revealed an HTLV-1B strain, found only in Central Africa, especially in Cameroon. Thus, ATLL may develop after HTLV-1 infection during adulthood, outside breastfeeding.


2018 ◽  
Vol 51 (2) ◽  
pp. 162-167 ◽  
Author(s):  
Erika Pedreira da Fonseca ◽  
Katia Nunes Sá ◽  
Rebeca Freitas Reis Nunes ◽  
Antônio Carlos Ribeiro Junior ◽  
Síntia Freitas Bastos Lira ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Mineki Saito ◽  
Charles R. M. Bangham

Human T-cell leukemia virus type-1 (HTLV-1) is a replication-competent human retrovirus associated with two distinct types of disease only in a minority of infected individuals: the malignancy known as adult T-cell leukemia (ATL) and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic progressive myelopathy characterized by spastic paraparesis, sphincter dysfunction, and mild sensory disturbance in the lower extremities. Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence from host population genetics, viral genetics, DNA expression microarrays, and assays of lymphocyte function suggests that complex virus-host interactions and the host immune response play an important role in the pathogenesis of HAM/TSP. Especially, the efficiency of an individual's cytotoxic T-cell (CTL) response to HTLV-1 limits the HTLV-1 proviral load and the risk of HAM/TSP. This paper focuses on the recent advances in HAM/TSP research with the aim to identify the precise mechanisms of disease, in order to develop effective treatment and prevention.


2002 ◽  
Vol 46 (9) ◽  
pp. 3080-3083 ◽  
Author(s):  
Emanuela Balestrieri ◽  
Giancarlo Forte ◽  
Claudia Matteucci ◽  
Antonio Mastino ◽  
Beatrice Macchi

ABSTRACT The effects of lamivudine (3TC) on in vitro infection of peripheral blood mononuclear cells (PBMC) from healthy donors with human T-cell lymphotropic virus type 1 (HTLV-1) were investigated. Direct measures of viral replication (viral DNA, RNA, and protein) all gave similar, very high 50% inhibitory concentrations in comparison with those previously reported for zidovudine. Nevertheless, 3TC inhibited HTLV-1-driven long-term growth of infected PBMC in vitro at concentrations (6.25 μM) which had poor or no direct antiviral effects, suggesting that another mechanism may be playing a role.


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