bims-nocaut 2024-04-07 papers

Issue of 2024–04–07
three papers selected by
Quentin Frenger, University of Strasbourg

Mol Microbiol. 2024 Apr 04.

LC3B labeling of the parasitophorous vacuole membrane of Plasmodium berghei liver stage parasites depends on the V-ATPase and ATG16L1.

Annina Bindschedler, Jacqueline Schmuckli-Maurer, Sophie Buchser, Tara D Fischer, Rahel Wacker, Tim Davalan, Jessica Brunner, Volker T Heussler.

The protozoan parasite Plasmodium, the causative agent of malaria, undergoes an obligatory stage of intra-hepatic development before initiating a blood-stage infection. Productive invasion of hepatocytes involves the formation of a parasitophorous vacuole (PV) generated by the invagination of the host cell plasma membrane. Surrounded by the PV membrane (PVM), the parasite undergoes extensive replication. During intracellular development in the hepatocyte, the parasites provoke the Plasmodium-associated autophagy-related (PAAR) response. This is characterized by a long-lasting association of the autophagy marker protein, and ATG8 family member, LC3B with the PVM. LC3B localization at the PVM does not follow the canonical autophagy pathway since upstream events specific to canonical autophagy are dispensable. Here, we describe that LC3B localization at the PVM of Plasmodium parasites requires the V-ATPase and its interaction with ATG16L1. The WD40 domain of ATG16L1 is crucial for its recruitment to the PVM. Thus, we provide new mechanistic insight into the previously described PAAR response targeting Plasmodium liver stage parasites.

Keywords: Plasmodium ; CASM; autophagy; host‐parasite interaction; liver stage

DOI: https://doi.org/10.1111/mmi.15259

Curr Opin Microbiol. 2024 Mar 29. pii: S1369-5274(24)00032-8. [Epub ahead of print]79 102456

Function of autophagy genes in innate immune defense against mucosal pathogens.

Xiaoyan Cui, Ya-Ting Wang.

Mucosal immunity is posed to constantly interact with commensal microbes and invading pathogens. As a fundamental cell biological pathway affecting immune response, autophagy regulates the interaction between mucosal immunity and microbes through multiple mechanisms, including direct elimination of microbes, control of inflammation, antigen presentation and lymphocyte homeostasis, and secretion of immune mediators. Some of these physiologically important functions do not involve canonical degradative autophagy but rely on certain autophagy genes and their 'autophagy gene-specific functions.' Here, we review the relationship between autophagy and important mucosal pathogens, including influenza virus, Mycobacterium tuberculosis, Salmonella enterica, Citrobacter rodentium, norovirus, and herpes simplex virus, with a particular focus on distinguishing the canonical versus gene-specific mechanisms of autophagy genes.

DOI: https://doi.org/10.1016/j.mib.2024.102456

Autophagy. 2024 Apr 02.

LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4+ T lymphocytes.

Baptiste Pradel, Guilhem Cantaloube, Marie Villares, Maïka S Deffieu, Véronique Robert-Hebmann, Vincent Lucansky, Mathias Faure, Nathalie Chazal, Raphaël Gaudin, Lucile Espert.

HIV-1 entry into CD4+ T lymphocytes relies on the viral and cellular membranes' fusion, leading to viral capsid delivery in the target cell cytoplasm. Atg8/LC3B conjugation to lipids, process named Atg8ylation mainly studied in the context of macroautophagy/autophagy, occurs transiently in the early stages of HIV-1 replication in CD4+ T lymphocytes. Despite numerous studies investigating the HIV-1-autophagy interplays, the Atg8ylation impact in these early stages of infection remains unknown. Here we found that HIV-1 exposure leads to the rapid LC3B enrichment toward the target cell plasma membrane, in close proximity with the incoming viral particles. Furthermore, we demonstrated that Atg8ylation is a key event facilitating HIV-1 entry in target CD4+ T cells. Interestingly, this effect is independent of canonical autophagy as ATG13 silencing does not prevent HIV-1 entry. Together, our results provide an unconventional role of LC3B conjugation subverted by HIV-1 to achieve a critical step of its replication cycle.

Keywords: Atg8ylation; CD4+ T lymphocyte; HIV-1; LC3B; virus entry

DOI: https://doi.org/10.1080/15548627.2024.2338573