How HIV-1 evades the antiviral immune response – CD96, an underestimated player in the immune system

It was already known that HIV evades our immune system by altering the composition of surface receptors on CD4+ T cells, the virus's primary target cells. However, exactly which receptors the virus manipulates had not been conclusively researched. To close this knowledge gap, the researchers isolated CD4+ T cells from human blood, infected the cells with HIV, and analyzed how the composition of surface receptors on the cells changes during HIV infection.

They discovered that HIV-infected CD4+ T cells have less CD96 than uninfected cells. CD96 is an immune receptor whose function in our immune system is still poorly understood. Its role in defending against viruses has also been little studied to date. The researchers showed that the function of CD96 has been underestimated to date. The protein plays an important role in the induction of a Th1- and Th17-associated antiviral immune response, which is primarily reflected in increased production of characteristic Th1 and Th17 cytokines. It is also interesting to note that HIV has developed a mechanism to block this CD96-mediated activation of the antiviral immune response. The virus uses two of its proteins for this purpose: Nef and Vpu.

The results of the study were published in Science Advances and can be found here.