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Can Blocking Nef Proteins Treat Immunodeficiency in HIV?

IMMUNODEFIENCY in patients with HIV may be counteracted by drugs that block protein kinases, according to a new study carried out by researchers at the University of Helsinki, Finland. It is understood that HIV cannot be eliminated from the body with the currently available medication and in 2018, approximately 38 million people were believed to be HIV-positive. The Nef protein, which is largely associated with HIV, promotes chronic immune activation and is the leading cause of immunodeficiency in patients with HIV and AIDS.

Antiviral drugs may be effective for suppressing the progression of HIV infection but they do not destroy the virus. In fact, the immune system in one-fifth of patients diagnosed with HIV does not recover fully. In some patients, the number of CD4 T cells remains low and insufficient, even after HIV in blood is suppressed following antiviral treatment. The study showed that the Nef protein may be produced in small quantities in the infected patients’ tissues over an extended period, despite the successful suppression of viral multiplication. Nef proteins activate the protein kinases that generate extracellular vesicles, which circulate the body via the blood and promote chronic immune activation. They are thought to cause a harmful chain of events through cellular signalling and are linked to increased pathogenicity as well as immunity-eroding activity.

Pharmaceutical agents in clinical use that inhibit protein kinases including Src, Raf, and MAPK were used by the researchers to investigate effectiveness on Nef proteins. The researchers studied these drugs in tissue culture and concluded that the current protein kinase inhibitors could completely stop the Nef protein from producing the inflammatory extracellular vesicles, which play a major role immunosuppression.

“Our findings make it possible to explore novel therapies without delay in patients whose immunodeficiency is not reversed to a sufficient degree with current antiretroviral therapies. The repurposing of kinase inhibitors for treating HIV infection appears to be a very promising way of solving this significant medical challenge,” said Prof Kalle Saksela, who led the research group from the university.