Identification of Vimentin as a Potential Therapeutic Target against HIV Infection

Viruses

Vladimir Besada¹  Viviana Falcon¹  Anna Ramírez¹  Hilda Garay¹  Carlos Duarte¹  Lila Castellanos-Serra¹  Osvaldo Reyes¹  Raimundo Ubieta¹  Lázaro Betancourt¹  Celia Fernández-Ortega¹  Dionne Casillas¹  Yassel Ramos¹  Taimi Paneque¹  Eladio Silva²  Leonor Navea²  Enrique Noa²  Marta Dubed² 

[1] Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanacán, Playa, P.O. Box 6162, Havana 10600, Cuba;Laboratory for AIDS Research, Carretera de Tapaste y Autopista Nacional, San José de las Lajas, Mayabeque CP 32700, Cuba;

关键词: leukocyte extract;    vimentin;    intermediate filaments;    cytoskeleton;    HIV;    anti-HIV activity;    proteomics;   

DOI  :  10.3390/v8060098

来源: DOAJ

【 摘 要 】

A combination of antiviral drugs known as antiretroviral therapy (ART) has shown effectiveness against the human immunodeficiency virus (HIV). ART has markedly decreased mortality and morbidity among HIV-infected patients, having even reduced HIV transmission. However, an important current disadvantage, resistance development, remains to be solved. Hope is focused on developing drugs against cellular targets. This strategy is expected to prevent the emergence of viral resistance. In this study, using a comparative proteomic approach in MT4 cells treated with an anti-HIV leukocyte extract, we identified vimentin, a molecule forming intermediate filaments in the cell, as a possible target against HIV infection. We demonstrated a strong reduction of an HIV-1 based lentivirus expressing the enhanced green fluorescent protein (eGFP) in vimentin knockdown cells, and a noteworthy decrease of HIV-1 capsid protein antigen (CAp24) in those cells using a multiround infectivity assay. Electron micrographs showed changes in the structure of intermediate filaments when MT4 cells were treated with an anti-HIV leukocyte extract. Changes in the structure of intermediate filaments were also observed in vimentin knockdown MT4 cells. A synthetic peptide derived from a cytoskeleton protein showed potent inhibitory activity on HIV-1 infection, and low cytotoxicity. Our data suggest that vimentin can be a suitable target to inhibit HIV-1.

【 授权许可】

Unknown