Integrase Inhibitors Effective against Human T-Cell Leukemia Virus Type 1
Open Access
- 1 May 2011
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 55 (5), 2011-2017
- https://doi.org/10.1128/aac.01413-10
Abstract
Drugs targeting the viral enzyme integrase have been in use for several years as part of the treatment regimen for patients with human immunodeficiency virus type 1 (HIV-1), and similar classes of compounds have been shown to inhibit human T-cell leukemia virus type 1 (HTLV-1) integration in vitro . The current study shows that the clinically approved HIV-1 integrase inhibitor, raltegravir, as well as the more recent diketo acid derivative, MK-2048, are active inhibitors of HTLV-1 infection in vitro . These agents were effective in inhibiting cell-free and cell-to-cell transmission of HTLV-1 in lymphoid and nonlymphoid cells. The drugs also inhibited HTLV-1 immortalization of human peripheral blood mononuclear cells. A novel adaptation of the Alu assay for viral integration was used to show that the drugs inhibit viral integration without affecting reverse transcription. These data support the administration of raltegravir and other integrase inhibitors as treatments for patients with HTLV-1-associated diseases.Keywords
This publication has 25 references indexed in Scilit:
- Retroviral intasome assembly and inhibition of DNA strand transferNature, 2010
- T-cell activation promotes tumorigenesis in inflammation-associated cancerRetrovirology, 2009
- Raltegravir, elvitegravir, and metoogravir: the birth of "me-too" HIV-1 integrase inhibitorsRetrovirology, 2009
- Human T Cell Leukemia Virus Reactivation with Progression of Adult T-Cell Leukemia-LymphomaPLOS ONE, 2009
- Inhibitors of Strand Transfer That Prevent Integration and Inhibit Human T-Cell Leukemia Virus Type 1 Early ReplicationAntimicrobial Agents and Chemotherapy, 2008
- HTLV-1 Integration into Transcriptionally Active Genomic Regions Is Associated with Proviral Expression and with HAM/TSPPLoS Pathogens, 2008
- Integrase and integration: biochemical activities of HIV-1 integraseRetrovirology, 2008
- Retroviral DNA Integration: Viral and Cellular Determinants of Target-Site SelectionPLoS Pathogens, 2006
- Basis of HTLV Type 1 Target Site SelectionAIDS Research and Human Retroviruses, 2000
- Seroprevalence of HTLV-I and HTLV-II among Intravenous Drug Users and Persons in Clinics for Sexually Transmitted DiseasesThe New England Journal of Medicine, 1992