SAMD9L acts as an antiviral factor against HIV-1 and primate lentiviruses by restricting viral and cellular translation - Archive ouverte HAL Access content directly
Journal Articles PLoS Biology Year : 2024

SAMD9L acts as an antiviral factor against HIV-1 and primate lentiviruses by restricting viral and cellular translation

Abstract

Sterile alpha motif domain-containing proteins 9 and 9-like (SAMD9/9L) are associated with life-threatening genetic diseases in humans and are restriction factors of poxviruses. Yet, their cellular function and the extent of their antiviral role are poorly known. Here, we found that interferon-stimulated human SAMD9L restricts HIV-1 in the late phases of replication, at the posttranscriptional and prematuration steps, impacting viral translation and, possibly, endosomal trafficking. Surprisingly, the paralog SAMD9 exerted an opposite effect, enhancing HIV-1. More broadly, we showed that SAMD9L restricts primate lentiviruses, but not a gammaretrovirus (MLV), nor 2 RNA viruses (arenavirus MOPV and rhabdovirus VSV). Using structural modeling and mutagenesis of SAMD9L, we identified a conserved Schlafen-like active site necessary for HIV-1 restriction by human and a rodent SAMD9L. By testing a gain-of-function constitutively active variant from patients with SAMD9L-associated autoinflammatory disease, we determined that SAMD9L pathogenic functions also depend on the Schlafen-like active site. Finally, we found that the constitutively active SAMD9L strongly inhibited HIV, MLV, and, to a lesser extent, MOPV. This suggests that the virus-specific effect of SAMD9L may involve its differential activation/sensing and the virus ability to evade from SAMD9L restriction. Overall, our study identifies SAMD9L as an HIV-1 antiviral factor from the cell autonomous immunity and deciphers host determinants underlying the translational repression. This provides novel links and therapeutic avenues against viral infections and genetic diseases.
Fichier principal
Vignette du fichier
published-journal.pbio.3002696.pdf (3.63 Mo) Télécharger le fichier
Origin Publisher files allowed on an open archive
Licence

Dates and versions

hal-04635756 , version 1 (04-07-2024)

Licence

Identifiers

Cite

Alexandre Legrand, Clara Dahoui, Clément de la Myre Mory, Kodie Noy, Laura Guiguettaz, et al.. SAMD9L acts as an antiviral factor against HIV-1 and primate lentiviruses by restricting viral and cellular translation. PLoS Biology, 2024, 22 (7), pp.e3002696. ⟨10.1371/journal.pbio.3002696⟩. ⟨hal-04635756⟩
0 View
0 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More