Identification of Vimentin as a Potential Therapeutic Target against HIV Infection

• Published in: Viruses Vol. 8; no. 6; p. 98
• Main Authors: Fernández-Ortega, Celia, Ramírez, Anna, Casillas, Dionne, Paneque, Taimi, Ubieta, Raimundo, Dubed, Marta, Navea, Leonor, Castellanos-Serra, Lila, Duarte, Carlos, Falcon, Viviana, Reyes, Osvaldo, Garay, Hilda, Silva, Eladio, Noa, Enrique, Ramos, Yassel, Besada, Vladimir, Betancourt, Lázaro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15.06.2016; MDPI
• Subjects: Acquired immune deficiency syndrome; AIDS; anti-HIV activity; Anti-HIV Agents - pharmacology; Antiretroviral therapy; Cell Line; Cytoskeleton; Disease transmission; Drug Discovery; Drug resistance; Drug therapy; Gene Knockdown Techniques; Genetic engineering; HIV; HIV Core Protein p24 - analysis; HIV Infections - drug therapy; HIV-1 - pathogenicity; HIV-1 - physiology; Host-Pathogen Interactions; Human immunodeficiency virus; Humans; Infections; intermediate filaments; leukocyte extract; Mass spectrometry; Mortality; Peptides; Proteins; Proteomics; Scientific imaging; vimentin; Vimentin - antagonists & inhibitors; Vimentin - metabolism; Virus Replication; Viruses; leukocyte extract; HIV; proteomics; cytoskeleton; vimentin; anti-HIV activity; intermediate filaments
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v8060098

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.