A joint team of researchers at the University of California, San Francisco, and others have discovered the molecular mechanism by which HIV, the human immunodeficiency virus that causes AIDS, escapes from the defenses of host cells.
After the initial HIV invasion into the human body, immune cells are gradually destroyed, making the body vulnerable to pathogen infection and causing various diseases. The medical community has shown that there is no treatment to completely eliminate HIV from the body, infected people need to continue to take antiviral drugs for treatment. As virus genes mutate, resistant viruses emerge that cannot be treated with drugs. So while HIV vaccines are being developed, new drugs for resistant viruses need to be developed.
Human cells have corresponding defenses against various viruses. For example, SAMHD1 is an enzyme produced by human cells that strongly blocks HIV-infected macrophages and T cells. On the other hand, the particles of hiv-2, which many infected people carry, contain a protein called VPX that breaks down SAMHD1 in the cells, causing hiv-2 to infect bone marrow cells.
Most viral proteins work with the help of "virus regulators" in human cells. They searched for VPX interacting proteins from more than 300 host proteins involved in phosphorylation and found that PIM kinase host proteins bind to VPX effectively and are specifically phosphorylated. Mass spectrometer analysis showed that serine, the 12th amino acid of VPX, was phosphorylated by PIM kinase. If the serine is replaced, the phosphorylation of VPX will not occur and the virus's replication ability will be reduced.
The results show that host PIM kinase is the factor that VPX ACTS on SAMHD1, and can effectively block the replication of hiv-2 by blocking PIM kinase.