Identification of Vimentin as a Potential Therapeutic Target against HIV Infection.
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.
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. celia.fernandez@cigb.edu.cu.
Celia
C
Fernández-Ortega
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. anna.ramirez@cigb.edu.cu.
Anna
A
Ramírez
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. dionne.casillas@cigb.edu.cu.
Dionne
D
Casillas
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. taimi.paneque@cigb.edu.cu.
Taimi
T
Paneque
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. raimundo.ubieta@cigb.edu.cu.
Raimundo
R
Ubieta
Laboratory for AIDS Research, Carretera de Tapaste y Autopista Nacional, San Jos&#233; de las Lajas, Mayabeque CP 32700, Cuba. cicdc@infomed.sld.cu.
Marta
M
Dubed
Laboratory for AIDS Research, Carretera de Tapaste y Autopista Nacional, San Jos&#233; de las Lajas, Mayabeque CP 32700, Cuba. riverora@infomed.sld.cu.
Leonor
L
Navea
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. lilacastellanos@infomed.sld.cu.
Lila
L
Castellanos-Serra
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. carlos.duarte@cigb.edu.cu.
Carlos
C
Duarte
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. viviana.falcon@cigb.edu.cu.
Viviana
V
Falcon
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. osvaldo.reyes@cigb.edu.cu.
Osvaldo
O
Reyes
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. hilda.garay@cigb.edu.cu.
Hilda
H
Garay
Laboratory for AIDS Research, Carretera de Tapaste y Autopista Nacional, San Jos&#233; de las Lajas, Mayabeque CP 32700, Cuba. eladio.silva@infomed.sld.cu.
Eladio
E
Silva
Laboratory for AIDS Research, Carretera de Tapaste y Autopista Nacional, San Jos&#233; de las Lajas, Mayabeque CP 32700, Cuba. enrnoa@infomed.sld.cu.
Enrique
E
Noa
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. yassel.ramos@cigb.edu.cu.
Yassel
Y
Ramos
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. vladimir.besada@cigb.edu.cu.
Vladimir
V
Besada
Center for Genetic Engineering and Biotechnology, Ave 31/158 and 190, Cubanac&#225;n, Playa, P.O. Box 6162, Havana 10600, Cuba. lazaro.betancourt@cigb.edu.cu.
Lázaro
L
Betancourt
D019380:Anti-HIV Agents / Q000494:pharmacology; D002460:Cell Line; D055808:Drug Discovery; D055785:Gene Knockdown Techniques; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D014746:Vimentin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014779:Virus Replication
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D014746:Vimentin
HIV; anti-HIV activity; cytoskeleton; intermediate filaments; leukocyte extract; proteomics; vimentin