Ujjwal Rathore, Paige Haas, Vigneshwari Easwar Kumar, Joseph Hiatt, Kelsey M Haas, Mehdi Bouhaddou, Danielle L Swaney, Erica Stevenson, Lorena Zuliani-Alvarez, Michael J McGregor, Autumn Turner-Groth, Charles Ochieng' Olwal, Yaw Bediako, Hannes Braberg, Margaret Soucheray, Melanie Ott, Manon Eckhardt, Judd F Hultquist, Alexander Marson, Robyn M Kaake, Nevan J Krogan
During HIV infection of CD4+ T cells, ubiquitin pathways are essential to viral replication and host innate immune response; however, the role of specific E3 ubiquitin ligases is not well understood. Proteomics analyses identified 116 single-subunit E3 ubiquitin ligases expressed in activated primary human CD4+ T cells. Using a CRISPR-based arrayed spreading infectivity assay, we systematically knocked out 116 E3s from activated primary CD4+ T cells and infected them with NL4-3 GFP reporter HIV-1. We found 10 E3s significantly positively or negatively affected HIV infection in activated primary CD4+ T cells, including UHRF1 (pro-viral) and TRAF2 (anti-viral)...
February 27, 2024: MBio