Annulate lamellae and intracellular pathogens

Abstract

Annulate lamellae (AL) have been observed many times over the years on electron micrographs of rapidly dividing cells, but little is known about these unusual organelles consisting of stacked sheets of endoplasmic reticulum-derived membranes with nuclear pore complexes (NPCs). Evidence is growing for a role of AL in viral infection. AL have been observed early in the life cycles of the hepatitis C virus (HCV) and, more recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), suggesting a specific induction of mechanisms potentially useful to these pathogens.Like other positive-strand RNA viruses, these viruses induce host cells membranes rearrangements. The NPCs of AL could potentially mediate exchanges between these partially sealed compartments and the cytoplasm. AL may also be involved in regulating Ca 2+ homeostasis or cell cycle control. They were recently observed in cells infected with Theileria annulata, an intracellular protozoan parasite inducing cell proliferation. Further studies are required to clarify their role in intracellular pathogen/ host-cell interactions.

Nup98 Is Subverted from Annulate Lamellae by Hepatitis C Virus Core Protein to Foster Viral Assembly

“…We then sought to determine if HCV core retrieves Nup98 alone or in combination with other proteins from the nuclear pore complex (NPC) or, alternatively, from annulate lamella (AL) pore complex (ALPC). The latter structures are discrete cytosolic double-membrane structures containing most components of the NPC, with the exception of some Nups such as TPR (also known as Megator/Mtor), a nuclear basket protein ( 10 ), and were identified in close proximity to HCV replication organelles ( 12 ). While these structures have mainly been identified by electron microscopy ( 22 ), recent studies indicated that RanBP2 (also known as Nup358) is a major constituent of ALPC ( 10 , 23 ), together with Nup98 ( 10 ), and that cytoplasmic RanBP2 staining could be considered a reliable AL marker ( 24 ).…”

“…Indeed, recent studies have shed light on AL composition ( 10 , 23 , 24 ), allowing us to detect them by fluorescence microscopy. The number of AL seems to be increased upon infection by several viruses, including hepatitis A virus ( 48 ), Japanese encephalitis virus ( 49 ), and SARS-CoV-2 ( 50 ), or appears to localize at close proximity to remodeled membranes induced by HCV ( 12 ); yet, their precise role was not characterized in these studies. It has also been proposed that AL could represent storage vesicles for viral glycoproteins in the case of human herpesvirus 6 ( 51 ).…”

“…The function of AL remains elusive; they could represent cytoplasmic deposits of excess of Nups or, alternatively, preassembled NPCs that could be rapidly mobilized to reform the nuclear envelope during mitosis ( 11 ). Interestingly, AL were observed by electron microscopy (EM) at early stages of HCV infection, in close proximity to the precursors of the double-membrane vesicles that allow replication of the HCV viral genome ( 12 ), but the precise role of these AL in HCV life cycle is still unknown.…”

Cellular Organelles Involved in Hepatitis E Virus Infection

“…The synthesis of approximately one-third of all cellular proteins is governed in this organelle [ 58 ]. As obligate parasites that solely rely on host machineries to thrive and produce progeny virions, almost all viruses usurp the endogenous functions of numerous ER-resident channels, chaperones, and enzymes throughout the whole viral life cycle [ 60 , 61 , 62 , 63 ]. Confocal imaging revealed that the overexpressed non-structural polyprotein pORF1 predominately co-localized with ER marker BAP31 [ 64 ], indicating that ER is likely to be a central organelle that governs HEV replication.…”

Nup358 regulates remodelling of ER-mitochondrial contact sites and autophagy

“…Many functions for AL have been proposed based on electron microscopic observations, which include roles in infection, cancers, gene expression, mRNA regulation and development (Kessel, 1992). AL are remodelled extensively during embryonic development, infection by intracellular pathogens including SARS-CoV-2 and in cancers (Eymieux et al, 2021;Kessel, 1992). Recently, involvement of AL in functional assembly of NPCs has been reported (Hampoelz et al, 2016).…”