The coxsackievirus and adenovirus receptor: virological and biological beauty

Abstract

The coxsackievirus and adenovirus receptor (CAR) is an essential multifunctional cellular protein that is only beginning to be understood. CAR serves as a receptor for many adenoviruses, human group B coxsackieviruses, swine vesicular disease virus, and possibly other viruses. While named for its function as a viral receptor, CAR is also involved in cell adhesion, immune cell activation, synaptic transmission, and signaling. Knockout mouse models were first to identify some of these biological functions; however, tissue‐specific model systems have shed light on the complexity of different CAR isoforms and their specific activities. Many of these functions are mediated by the large number of interacting proteins described so far, and several new putative interactions have recently been discovered. As antiviral and gene therapy strategies that target CAR continue to emerge, future work poised to understand the biological implications of manipulating CAR in vivo is critical.

Cryo-EM structures reveal the molecular basis of receptor-initiated coxsackievirus uncoating

“…Picornaviruses infect host cells by binding to membrane receptors and undergoing receptor-mediated endocytosis (Baggen et al, 2018b;Marsh and Helenius, 2006). Numerous enterovirus receptors have been identified, and are classified into either attachment or uncoating receptors based on their involvement in cell entry or genome release, respectively (Baggen et al, 2018a;Bergelson et al, 1994;He et al, 2001;Mendelsohn et al, 1989;Sun et al, 2020;Zhang et al, 2008;Zhao et al, 2019, 2020, Zhou et al, 2019. Attachment receptors facilitate virus attachment to host cells and promote virus uptake.…”

Antigen Presentation of mRNA-Based and Virus-Vectored SARS-CoV-2 Vaccines

“…Normally, adenoviruses attach to membrane receptors. Ad5 will bind to the so-called coxsackievirus and adenovirus receptor CAR, which belongs to the Ig superfamily of proteins present in nearly every human cell and whose normal function is just being discovered [ 72 ]. Via clathrin-coated pits, the virus is taken into the cells, and after rupture of the endosome, viral particles are dispersed into the cytoplasm.…”

Adenovirus Type 6: Subtle Structural Distinctions from Adenovirus Type 5 Result in Essential Differences in Properties and Perspectives for Gene Therapy

“…It is interesting to note that because tight junctions localize in basolateral, but not apical, surfaces of polarized epithelial cells, Ad6 and other viruses are hindered in their access to bind their primary receptors and infect these cells. However, there is a particular isoform of CAR which does localize on apical surfaces and can be used as a receptor for Ad entering from the airway lumen [28]. Additionally, the apical localization of this CAR isoform is facilitated by pro-inflammatory cytokines produced by alveolar macrophages after endocytosis of Ads [29].…”