Viral escape from endosomes and host detection at a glance

Abstract

In order to replicate, most pathogens need to enter their target cells. Many viruses enter the host cell through an endocytic pathway and hijack endosomes for their journey towards sites of replication. For delivery of their genome to the host cell cytoplasm and to avoid degradation, viruses have to escape this endosomal compartment without host detection. Viruses have developed complex mechanisms to penetrate the endosomal membrane and have evolved to co-opt several host factors to facilitate endosomal escape. Conversely, there is an extensive variety of cellular mechanisms to counteract or impede viral replication. At the level of cell entry, there are cellular defense mechanisms that recognize endosomal membrane damage caused by virus-induced membrane fusion and pore formation, as well as restriction factors that block these processes. In this Cell Science at a Glance article and accompanying poster, we describe the different mechanisms that viruses have evolved to escape the endosomal compartment, as well as the counteracting cellular protection mechanisms. We provide examples for enveloped and non-enveloped viruses, for which we discuss some unique and unexpected cellular responses to virus-entry-induced membrane damage.

Extracellular Vesicles Enriched with Moonlighting Metalloproteinase Are Highly Transmissive, Pro-Tumorigenic, and Trans-Activates Cellular Communication Network Factor (CCN2/CTGF): CRISPR against Cancer

“…Thus, the LuM1-derived oncosomes could contain MMP3 and CD326/EpCAM, whose transfer may induce stemness in recipient cells in the local tumor microenvironment and distant organs. There are two potential mechanisms of MMP3 transmission, including (i) six basic amino acid clusters as functional NLS in MMP3 [28,29], which could work as endosomal membrane-permeable, membrane-disrupting translocase/flippases as in the Trans-Activator of Transcription Protein (TAT) peptide, also called the Cell-Penetrating Peptide (CPP) [54]; and/or (ii) proteolysis-dependent endosomal escape, a mechanism seen in other proteinases such as cathepsins that are essential for the endosomal escape of viruses [55,56]. Thus, MMP3 protease activity may promote EV transmission and invasion into cells by degrading ECM, cell surface receptors, and cytoskeletal proteins on/in recipient cells.…”

Lessons learned from adenovirus (1970–2019)

“…This process could ultimately lead to an alteration of the composition of sphingolipids in the endosomal membrane and membrane destabilization. Further analysis of these biochemical events may help improve our understanding of how adenovirus, as well as other nonenveloped viruses , achieve membrane penetration during cell entry.…”

Two‐pore channels regulate Tat endolysosome escape and Tat‐mediated HIV‐1 LTR transactivation

“…[80][81][82][83] Once endocytosed, viruses can be degraded by pH-sensitive hydrolytic enzymes in endolysosomes or alternatively they can escape the endolysosomes following which they can transit to the nucleus or recycled back into the extracellular space. 84 Similar to viruses, secreted viral proteins from infected cells can also enter cells via endocytosis. For instance, released HIV-1 viral proteins gp120 85,86 and Tat [24][25][26][27] have been shown to enter cells via endocytosis, where they can exert direct cytotoxic effects.…”