MELK implicated in HIV-1 infection
Today, HIV is a significant health threat to people of all ages on all continents around the world. The virus can be classified into two types, HIV-1 and HIV-2. HIV-1 is more common, accounting for about 95% of all infections worldwide.
According to a study published 6 July 2017 in PLoS Pathogens, a host protein called MELK plays a key role in early infection of HIV-1. Led by researchers from Tokyo Medical and Dental University (TMDU), the study suggests MELK as a new therapeutic target against HIV infection.
During viral infection, a virus needs to remove its protein coat and inject its genetic material into a host cell, so that the virus can replicate its own DNA for making new viral particles.
TMDU researchers set out to determine host factors implicated in HIV-1 infection. Using a genome-wide RNAi screen and other analytic approaches, they found that the MELK protein produced by host cells is required for HIV-1 replication. Although HIV-1 was able to enter MELK-depleted cells, it failed to remove its coat properly. As a result, the virus could not effectively replicate its DNA in these MELK-depleted cells.
The team also tested the effect of the small-molecule MELK inhibitor OTSSP167 on HIV-1 replication. The results showed that OTSSP167 markedly inhibited HIV-1 replication in host cells in a dose-dependent manner.
MELK, or maternal embryonic leucine zipper kinase, is an enzyme that regulates intracellular signaling and influences many cellular activities. This study showed that the catalytic activity of MELK modulates HIV-1 replication. MELK can modify the protein coat of HIV-1, and this modification triggers coat removal (or called uncoating), which is important for viral replication.
Collectively, the study identifies MELK as a key host factor involved in HIV-1 replication and suggests that small-molecule inhibitors of MELK may hold promise for combating HIV-1 infection.
The study is conducted in collaboration with researchers from Kyoto University, Tokyo University of Technology, National Institute of Infectious Diseases, and Shionogi & CO., LTD. Hiroaki Takeuchi from TMDU is the first author.
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