Vpu protein has a stronger effect on immune suppression than previously thought

In early February, eLife magazine published the results of a study by a group of specialists from Germany and the United States who established the more important role of HIV-1-produced Vpu protein in suppressing the immune system's response to infection. The findings of scientists can help develop more effective methods of treating HIV, including strategies aimed at activating latent strains.

According to researchers, despite the considerable efforts of the immune system spent on the fight against HIV, the virus still finds an opportunity to effectively multiply and spread.

This “success” can be partially explained by the work of a number of viral factors that introduce the immune system “into error”. These include four "auxiliary proteins" - Vif, Nef, Vpr and Vpu.

“When cells are infected with HIV, they can send alarm signals to healthy cells, urging them to fight viral pathogens and thereby prevent the spread of infection. However, the extra protein U (Vpu) can drown out these signals, ”explains study co-author Simon Langer.

“[We] already knew that Vpu uses several methods to suppress the immune response to HIV infection. However, the collected data showed that this protein plays a much greater role by inhibiting the activation of other proteins, called transcription factors, - adds co-author Christina Hopfensperger, - Therefore, our main task was to learn more about the mechanisms used by Vpu to achieve this goal. ” .

A group of scientists analyzed human cells affected by artificially created HIV-1 strains that generated defective Vpu. After that, biologists checked the effect of these proteins on the immune response, the passage of alarm signals and the production of antiviral agents by the cells.

The results showed that Vpu suppresses the activation of a transcription factor called NF-κB, the “main regulator” of immune activation in infected people. As a result of a decrease in the activity of NF-κB, Vpu reduced the level of generation of a number of cellular agents that play a key role in the antiviral immune response.

“Indeed, we saw that in the event of HIV being infected without Vpu, processes are being released to release more interferons, which is an important alarm signal for uninfected cells,” Christian Hummer commented on the findings of experts. connections between immune cells during HIV infection. "

"In general, we showed that Vpu plays a much more significant role in suppressing the immune system than previously thought, especially because it interferes with NF-κB-induced immune responses at the transcription level," concluded Dr. Souter, one of the team leaders. Center of Ulm University.

“Inactive NF-κB can keep HIV at rest, which prevents the virus from being eradicated with modern drugs. Thus, our results can serve as a basis for therapeutic approaches aimed at activating latent HIV strains for subsequent elimination of the virus. ”