Abstract
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.
Highlights
Despite notable advances made during the last decade on antiretroviral therapies against the human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS) continues to rank among the top 10 causes of death worldwide, and still represents the second most important cause of mortality in low-income countries [1]
We demonstrate that modifying the levels of endogenous vimentin or the structure of vimentin intermediate filaments (IFs) lead to the inhibition of HIV replication
HIV-1 Inhibition and Downmodulation of Vimentin in MT4 Cells Treated with an Anti-HIV Fraction
Summary
Despite notable advances made during the last decade on antiretroviral therapies against the human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS) continues to rank among the top 10 causes of death worldwide, and still represents the second most important cause of mortality in low-income countries [1]. Current treatment guidelines for HIV disease recommend the use of antiretroviral drug (ARVs) regimes that combine at least two, and preferably three, drugs from two or more drug classes to achieve viral suppression [4]. This combination is known as highly active antiretroviral therapy (HAART) or antiretroviral therapy (ART) [5,6]. The use of the ART is fundamentally limited by the development of viral resistance [10], and in addition, ART has been associated with bone, cardiovascular and cognitive disorders, does not eliminate viral reservoirs, and requires lifelong daily therapy [11,12]
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