Inhibition of Cell-to-Cell Transmission of Human T-Cell Lymphotropic Virus Type 1 In Vitro by Carbohydrate-Binding Agents

Abstract

Peripheral blood mononuclear cells (PBMCs) from healthy individuals can be infected by human Tlymphotropic virus type 1 (HTLV-1) upon cocultivation of the PBMCs with irradiated HTLV-1-transformed human MT-2 cells. This model system closely mimics HTLV-1 transmission through cell-to-cell contact.Carbohydrate-binding agents (CBAs) such as the ␣(1,3)/␣(1,6)mannose-specific Hippeastrum hybrid agglutinin and the GlcNAc-specific Urtica dioica agglutinin, and also the small, nonpeptidic ␣(1,2)-mannose-specific antibiotic pradimicin A, were able to efficiently prevent cell-to-cell HTLV-1 transmission at nontoxic concentrations, as evidenced by the lack of appearance of virus-specific mRNA and of the viral protein Tax Human T-lymphotropic virus type 1 (HTLV-1) is a member of the genus Deltaretrovirus of the family Retroviridae and is associated with various pathologies (35). The most common characterized pathologies are oncological transformation (i.e., adult T-cell leukemia [ATL] and cutaneous T-cell lymphoma) and neurological abnormalities (i.e., tropic spastic paraparesis). The virus is spread in areas of endemicity in Japan, Central America, and South America. Its worldwide spread encompasses around 20 million infected individuals (12,13,26). The main routes of HTLV-1 infection in vivo consist of mother-to-infant transmission (mainly through breast-feeding), parenteral infection, and viral transmission through sexual intercourse (20,26,27). HTLV-1 infection occurs predominantly by infection of CD4 ϩ T lymphocytes, followed by random integration of the provirus into the cellular genome (11). HTLV-1 infection in vivo results in a lifelong infection that is characterized by low, if any, viremia. Therefore, in the absence of a sustained extracellular phase during the replication cycle of HTLV-1, survival and propagation of the virus within the host seem to be mainly ensured by two modalities: (i) the reverse transcriptase (RT)-independent mitotic pathway and (ii) cell-to-cell contacts allowing the virus to migrate from infected to uninfected cells through an RT-dependent route. However, the mechanisms involved in the entry of HTLV-1 into the cell have not been fully elucidated. HTLV-1 transmission benefits from the formation of cellular conjugates through the generation of biological synapses and involvement of the cytoskeleton (17). Although the glucose transporter GLUT-1 has been identified as a cellular receptor for HTLV-1 (22), other studies indicate that the interaction with this receptor is not sufficient by itself for viral entry into the cell (18,29). The structural component of HTLV-1 presumably required for receptor recognition is composed of the envelope glycoprotein (gp46) and a noncovalently associated transmembrane anchor protein (gp21), derived from a common gp63 precursor (21). gp46 is among the smallest retroviral envelope proteins known, and it exhibits little sequence variability (19). Studies have revealed that all four potential N-glycosylation sites (28) in gp46 are used and that the glycans are m...

Pentosan Polysulfate Demonstrates Anti-human T-Cell Leukemia Virus Type 1 ActivitiesIn VitroandIn Vivo

“…Moreover, similar results were obtained by coculturing JETWT35 cells with MT-2 cells ( Fig. 4C), which is another donor cell line widely used for HTLV-1 infection (38)(39)(40)(41)(42)(43). Interestingly, this inhibition of HTLV-1 transmission by PPS became inefficient when PPS was added to the coculture 12 h later ( Fig.…”

“…To this end, we used human umbilical vascular endothelial cells (HUVEC) because they are primary cells that resemble BBB cells and can be infected by HTLV-1 (44,45). We used lethally irradiated MT-2 cells as the donor cells to infect HUVEC, which is a widely used method of HTLV-1 infection (38)(39)(40)(41)(42). We first confirmed that there were no viable MT-2 cells 3 days after lethal irradiation by a trypan blue exclusion assay (data not shown).…”

Evaluación serológica y virológica de la infección del virus linfotrópico humano 1 en grupos familiares de Tumaco, Colombia

“…However, it remains to be determined whether those lymphocytes circulate for longer in saliva or are newly deposited in saliva and milk by leaking from microcirculation as has been reported previously (32)(33)(34)(35). There is some indirect evidence, both from our own study and previous work for HTLV-1 infection of oral mucosa by cellto-cell contact with circulating T cells, primarily through breast-feeding (32,(36)(37)(38).…”

Potential of carbohydrate‐binding agents as therapeutics against enveloped viruses

“…4 These CBAs are also active against infection of certain viruses of the Nidovirales family, like coronaviruses, 4,7,202 arteriviruses, and toroviruses, 8 and against CMV, 66 the feline immunodeficiency virus 203 and DENV 6 infection and cell-to-cell transmission of HTLV-1. 204 CV-N has also been found inhibitory to Ebola virus and influenza virus. 44,205 Conflicting reports, however, exist on the potential of CBAs to inhibit HSV entry.…”