One step closer to eliminating the latency of the AIDS virus

Human Immunodeficiency Virus (HIV) infections, if left untreated, lead to AIDS, the gradual destruction of the immune system. Worldwide, some 650,000 people die each year from AIDS, making it a serious threat to human health. However, although there is no general cure for an established infection, adequate antiretroviral therapy allows HIV-positive people to lead relatively healthy lives. Unfortunately, once treatment is discontinued, the virus reappears from a reservoir of latently infected cells.

An international study coordinated by Andreas Meyerhans and Juana Díez, from Pompeu Fabra University (UPF) in Barcelona, ​​has identified and characterized Schlafen 12 (SLFN12), a new HIV restriction factor that could lead the way to new strategies to cure HIV. infection.

Specifically, SLFN 12 stops the production of viral proteins and helps virus-infected cells escape anti-HIV therapy and immune responses.

“Latency is a major barrier to virus clearance in HIV-infected people. We won’t be able to cure an existing infection until we get rid of latently infected cells. That’s why it’s essential to understand how latency works.” explains Meyerhans.

The SLFN12 protein restricts the production of viral proteins by cleaving specific cellular tRNAs, the building blocks for protein construction. As a consequence, in the presence of active SLFN12, HIV-infected CD4 T cells are unable to complete the virus production process, but instead keep their templates, HIV RNA, in a latent state.

Members of the UPF Infection Biology Research Group. (Photo: UPF)

“SLFN12 prevents the production of proteins, restricting the production of viral particles. Such cells are latently infected, invisible to the immune system and to anti-HIV therapies,” says Mie Kobayashi-Ishihara, co-author of the study.

The study also reveals how SLFN12 can specifically inhibit HIV protein production without blocking cellular protein production. “SLFN12 cleaves the Leucine-UUA tRNA, a building block that is rarely used for cellular proteins but is essential for HIV viral proteins,” explains Juana Díez.

This finding opens the possibility of designing new therapeutic strategies against HIV. “Blocking the antiviral functions of SLFN12 should increase the expression of viral proteins and thus allow the host’s immune system and antiviral drugs to better clear viral reservoirs,” explains Meyerhans.

The study is titled “Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells”. And it has been published in the academic journal Communications Biology. (Source: UPF)