Gladstone Institutes Unveils First Genome-Wide Roadmap of Human-HIV Gene Interactions in Primary T Cells

Researchers create the first comprehensive genetic roadmap of HIV interactions in human T cells. Discover the new proteins PI16 and PPID that block the virus.

By: AXL Media

Published: Apr 21, 2026, 4:46 AM EDT

Source: Information for this report was sourced from Gladstone Institutes

Mapping the Hijacking of Human Machinery

Despite decades of intensive research, the specific human genes that allow HIV to thrive or fail within a host remained partially obscured. HIV is famously efficient, using only nine genes to dismantle and reorganize the human immune system. A new study led by Dr. Alex Marson at the Gladstone-UCSF Institute of Genomic Immunology has finally provided a comprehensive genetic roadmap of these interactions. By moving beyond "immortalized" cancer cell lines and utilizing primary CD4+ T cells—the virus's actual target in the human body—the team has identified a vast network of proteins that determine the trajectory of an infection.

The Breakthrough in Primary Cell Infection

Historically, studying HIV in real human T cells was hampered by low infection rates in laboratory settings, often as low as one percent. Researchers in the Marson lab, including Dr. Ujjwal Rathore, spent a decade optimizing this process, eventually achieving infection rates of up to 70 percent. This technical milestone allowed the team to leverage CRISPR gene editing to test all 20,000 human genes simultaneously. By disrupting every gene to find what the virus needs, and separately over-activating genes to find what the virus fears, the team surfaced "invisible" antiviral proteins that the virus typically silences during a standard infection.

Discovery of PI16 and PPID as Potent Defenders

The screening process highlighted two proteins, PI16 and PPID, which had never before been associated with HIV. The researchers discovered that PI16 functions as a high-level gatekeeper, preventing the virus from fusing with the T cell membrane and stopping the infection at the threshold. Conversely, PPID operates within the cell, interfering with the virus’s ability to reach the nucleus and replicate its genetic material. In laboratory tests, the team was able to modify PPID to be ten times more effective at halting the virus, demonstrating its potential as a target for future therapeutic enhancement.