One step closer to eliminating latency, the real challenge in combating HIV

Newswise — A worldwide research conducted by MELIS-UPF scientists from the Infection Biology and Molecular Virology departments has detected and defined Schlafen 12 (SLFN 12) as a new HIV limiting element. SLFN 12 terminates the generation of viral proteins and aids cells infected with the virus to evade anti-HIV therapy and immune reactions. These discoveries open the path for enhancing therapeutic methods that strive to heal HIV infections.

If HIV infections are not treated, they cause a progressive deterioration of the immune system, leading to Acquired Immunodeficiency Syndrome (AIDS) in its advanced stages. AIDS is a significant threat to global health, causing around 650,000 deaths annually. While there is no universal cure for a confirmed infection, suitable antiretroviral therapy allows individuals living with HIV to have a relatively healthy lifestyle. Unfortunately, after discontinuing treatment, the virus reappears from a latent reservoir of infected cells.

"Latency presents a significant obstacle that hinders the eradication of the virus in individuals infected with HIV. Eliminating latently infected cells is imperative to cure a pre-existing infection. Therefore, comprehending how latency functions is crucial," states Andreas Meyerhans, ICREA research professor at UPF, who, along with Juana Díez, led the study.

The research paper, which was published in Communication Biology, has discovered and defined SLFN12, a protein that inhibits the production of viral proteins by fragmenting specific cellular tRNAs, which are the fundamental units for constructing proteins. Consequently, when SLFN12 is active, CD4 T cells infected with HIV are unable to finish the virus production process but maintain its templates, HIV RNA, in a dormant state.

"SLFN12 hampers protein synthesis, curbing the generation of viral particles. As a result, such cells become latently infected, remaining undetectable by the immune system and anti-HIV therapies," explains Mie Kobayashi-Ishihara, the first author of the research paper.

The research study also discloses how SLFN12 can selectively obstruct HIV protein production without impeding cellular protein production. "SLFN12 fragments Leucine-UUA tRNA, a fundamental unit that is seldom utilized for cellular proteins but is critical for the generation of HIV viral proteins," elucidates Juana Díez.

This discovery presents the opportunity to develop novel therapeutic approaches against HIV. "Obstructing the antiviral activities of SLFN12 should heighten the expression of viral proteins and, therefore, empower the host immune system and antiviral drugs to eliminate viral reservoirs more effectively. Once virus production resumes, it becomes detectable again, and we can target it, with the hope of completely eradicating latently infected cells," concludes Meyerhans.

Schlafen is a German word meaning “sleeping” that gives its name to a family of proteins involved in cancer, drug sensitivity and antiviral functions.