Novel strategy successfully suppresses HIV infection in mice

A new method, called synapse for T-cell activation (synTac), can attack HIV-infected T cells and may be a new cure for HIV and other diseases.

HIV cells

A team at the Albert Einstein College of Medicine, US, has developed a strategy to suppress HIV infections in mice, offering a path to a functional cure for HIV and other chronic viral infections. 

HIV infects the immune system’s CD4+ T cells. For the past 25 years, people infected with HIV have been able to control their infection through antiretroviral therapy (ART) – a combination of several drugs that prevent the virus from infecting new CD4+ T cells and multiplying within them. “Although ART works remarkably well at keeping HIV in check indefinitely, it is a stalemate and not a checkmate,” explained co-corresponding author Professor Harris Goldstein.

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The research, published in The Journal of Clinical Investigation, involved proteins designed to selectively stimulate the immune system’s CD8+ “killer” T cells to multiply and specifically attack infected T cells. Co-corresponding author Dr Steven Almo developed the synthetic proteins, known as synTac, short for “synapse for T-cell activation”.

According to Goldstein, their study showed that synTac proteins, by greatly boosting the quantity of protective HIV-specific CD8+ T cells, were able to eliminate these infected cells. “It is unlikely that any treatment strategy can remove all latently infected T cells,” said Goldstein. “Our goal with synTac is a ‘functional cure,’ in which the powerful immune response induced by synTac suppresses HIV to undetectable levels even after they discontinue ART.”

The researchers first tested their synTac proteins on human blood samples infected with either HIV or cytomegalovirus (CMV), a common type of herpes virus that can infect and kill immunosuppressed patients. For blood from human donors infected with either HIV or CMV, synTacs specific for mobilising immune responses against those viruses triggered selective and vigorous multiplication of CD8+ T cells that exhibited potent HIV or CMV anti-viral activity.

Next, the researchers intravenously injected synTacs specific for HIV or CMV into virus-infected mice with “humanised” immune systems that permit infection by viruses affecting people, such as HIV and CMV. The synTac proteins triggered human HIV-specific CD8+ T cells to increase 32-fold and increased human CMV-specific CD8+ T cells by 46-fold. In both the HIV- and CMV-infected mice, the large numbers of synTac-stimulated human CD8+ T cells potently suppressed the viral infections, suggesting that synTacs may offer new opportunities for functionally curing HIV and treating CMV and other viral infections.

“A key asset of the synTac platform is how easily we can programme synTac proteins to combat any of the many diseases in which T cells play a role – including disease targets that extend well beyond viruses,” commented Almo. “For example, an ongoing clinical trial involving patients with head and neck cancer is assessing synTac’s ability to selectively activate anti-cancer T cells. Since synTacs can turn off, as well as activate T cells, they are also under study for treating type 1 diabetes and other autoimmune diseases by turning off T cells that mistakenly attack people’s healthy tissues.” 

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