Abstract
Viral life cycles consist of three main phases: (1) attachment and entry, (2) genome replication and expression, and (3) assembly, maturation, and egress. Each of these steps is intrinsically reliant on host cell factors and processes including cellular receptors, genetic replication machinery, endocytosis and exocytosis, and protein expression. Annexin A2 (AnxA2) is a membrane-associated protein with a wide range of intracellular functions and a recurrent host factor in a variety of viral infections. Spatially, AnxA2 is found in the nucleus and cytoplasm, vesicle-bound, and on the inner and outer leaflet of the plasma membrane. Structurally, AnxA2 exists as a monomer or in complex with S100A10 to form the AnxA2/S100A10 heterotetramer (A2t). Both AnxA2 and A2t have been implicated in a vast array of cellular functions such as endocytosis, exocytosis, membrane domain organization, and translational regulation through RNA binding. Accordingly, many discoveries have been made involving AnxA2 in viral pathogenesis, however, the reported work addressing AnxA2 in virology is highly compartmentalized. Therefore, the purpose of this mini review is to provide information regarding the role of AnxA2 in the lifecycle of multiple epithelial cell-targeting viruses to highlight recurrent themes, identify discrepancies, and reveal potential avenues for future research.
Highlights
To successfully replicate, viruses must hijack and reprogram host cells to produce viral progeny
By addressing the involvement of Annexin A2 (AnxA2) in the context of multiple viruses and viral life cycle stages, we offer a broad perspective on an emerging host–pathogen interaction and highlight the complexities in AnxA2 biology
AnxA2 exists as a monomer localized to the cytoplasm, vesiclebound, or as a heterotetrameric complex termed AnxA2/S100A10 heterotetramer (A2t) consisting of two AnxA2 monomers bridged by an S100A10 dimer found on the inner and outer leaflet of the plasma membrane
Summary
Viruses must hijack and reprogram host cells to produce viral progeny. AnxA2 is utilized by HPV, enterovirus 71 (EV71), respiratory syncytial virus (RSV), and cytomegalovirus (CMV) during cell attachment and penetration (Wright et al, 1994, 1995; Raynor et al, 1999; Malhotra et al, 2003; Derry et al, 2007; Yang et al, 2011; Woodham et al, 2012, 2015; Dziduszko and Ozbun, 2013; Taylor et al, 2018), by hepatitis C virus (HCV) and influenza A virus (IAV) during replication (LeBouder et al, 2008; Backes et al, 2010; Saxena et al, 2012; Ma et al, 2017; Solbak et al, 2017), and by measles virus (MV) during assembly and maturation (Koga et al, 2018).
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