Genome-scale imaging-based approach may help identify previously unknown human proteins that HIV degrades to enhance its infection process, finds a new study.
Highlights
- New Global Arrayed Protein Stability Analysis (GAPSA) can help identify HIV circuits that drive the destruction of healthy human proteins in cells.
- HIV-1 accessory proteins Vpu usually degrade human proteins to enhance its infection process.
- Identifying Vpu target proteins can help find new drugs that block the interaction, potentially preserve host anti-viral proteins and limit HIV infection.
Vpu is HIV's weapon against the innate immune response--the body's first line of defense against pathogens. Vpu triggers the degradation of host proteins meant to protect against HIV infection, thereby helping the virus overcome barriers to infection and replication.
"In this study we screened a set of 433 interferon-stimulated genes (ISGs)--genes that become activated in response to infection--against Vpu to create a more comprehensive list of HIV's cellular targets," says Lars Pache, Ph.D., staff scientist in Chanda's lab and co-author of the paper.
"Identifying Vpu target proteins creates an opportunity to find new drugs that block the interaction, potentially preserving host anti-viral proteins and limiting HIV infection. Importantly, the system can be equally applied to other infectious diseases that evade the immune system, such as Ebola, influenza, Zika, and others," explains Pache.
"To our knowledge, GASPA is the first cell-based array platform that screens for regulators of the building and turnover of proteins (proteostasis). In addition to providing critical knowledge of how cells work, the technology can be applied to identify protein degraders that specifically target disease-causing proteins, which can open new therapeutic opportunities for a multitude of diseases," says Chanda.
"Our next step(s) is to collaborate with scientists across other disease areas to identify these molecular circuits that regulate protein stability," Chanda says. "We plan to use the technology to comprehensively catalog pairs of all human proteins known to regulate degradation and their cellular targets. We anticipate that this compendium of activities will expand the therapeutic landscape for many diseases."
- Prashant Jain, Guney Boso, Simon Langer,et.al.Large-Scale Arrayed Analysis of Protein Degradation Reveals Cellular Targets for HIV-1 Vpu, Cell Reports (2018).DOI: https://doi.org/10.1016/j.celrep.2018.01.091 Link
Source-Eurekalert