Researchers discovered that interferon-stimulated SAMD9L restricts HIV-1 and other lentiviruses by inhibiting viral translation and endosomal trafficking, while SAMD9 enhances HIV-1 replication.
By Dr. Sushama R. Chaphalkar, PhD.Reviewed by Susha Cheriyedath, M.Sc.Jul 7 2024 In a recent study published in the journal PLOS Biology, researchers in France investigated the cellular function and antiviral role of human SAMD9L and its paralog SAMD9 in HIV -1 restriction. They found that interferon -stimulated human SAMD9L inhibits HIV -1 and primate lentiviruses in late replication phases, impacting viral translation and endosomal trafficking, while paralog SAMD9 enhances HIV -1 replication.
SAMD9 and SAMD9L act as restriction factors for poxviruses by repressing viral translation. However, their role in restricting other viruses, such as HIV-1, remains largely unexplored. HIV-1, a major cause of acquired immunodeficiency syndrome , continues to be a significant public health issue. Identifying host proteins that inhibit HIV-1 and understanding their involvement in cellular functions can inform the development of new therapeutic targets against viral infections and genetic diseases.
Results and discussion SAMD9L was found to inhibit HIV-1 infectious virus yield, while SAMD9 was found to enhance it. SAMD9L was found to strongly restrict HIV-1 transmitted/founder strains in a dose-dependent manner, independent of coreceptor use. SAMD9L also restricted HIV-2, SIVagm.Tan1 and SIVmac but did not affect MLV, MOPV, or VSV, indicating a specific antiviral effect on lentiviruses.
Mutating E198/D243 was found to abolish SAMD9L's ability to inhibit cellular protein synthesis. These findings highlight the critical role of the SLFN-like active site in SAMD9L's regulation of both cellular and viral protein production. Additionally, Western blot analysis revealed the viral-specific interactions of SAMD9L.
HIV-1 Protein Apoptosis Ataxia Cell Cell Division ELISA Gene Genes Genetic Immunodeficiency Interferon Mutation Myelodysplasia Pancytopenia Protein Expression RNA Stress Translation Virus Western Blot
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