Human adenovirus binding to host cell receptors: a structural view

Abstract

Human Adenoviruses (HAdVs) are a family of clinically and therapeutically relevant viruses. A precise understanding of their host cell attachment and entry mechanisms can be applied in inhibitor design and the construction of targeted gene delivery vectors. In this article, structural data on adenovirus attachment and entry are reviewed. HAdVs engage two types of receptors: first, an attachment receptor that is bound by the fibre knob protein protruding from the icosahedral capsid, and next, an integrin entry receptor bound by the pentameric penton base at the capsid vertices. Adenoviruses use remarkably diverse attachment receptors, five of which have been studied structurally in the context of HAdV binding: Coxsackie and Adenovirus Receptor, CD46, the glycans GD1a and polysialic acid, and desmoglein-2. Together with the integrin entry receptors, they display both symmetrical and asymmetrical modes of binding to the virus as demonstrated by the structural analyses reviewed here. The diversity of HAdV receptors contributes to the broad tropism of these viruses, and structural studies are thus an important source of information on HAdV-host cell interactions. The imbalance in structural data between the more and less extensively studied receptors remains to be addressed by future research.

Virus-Induced Changes of the Respiratory Tract Environment Promote Secondary Infections With Streptococcus pneumoniae

“…Other viruses that predispose the host for secondary bacterial infections include respiratory syncytial virus (RSV), rhinovirus (RV), human coronavirus, parainfluenza virus and adenovirus (AV) ( Falsey et al., 2013 ). Whereas parainfluenza virus also uses host sialic acids to attach to cells, syncytial virus, rhinovirus, parainfluenza virus and adenovirus utilize diverse attachment receptors ( Moscona, 2005 ; Bochkov and Gern, 2016 ; Battles and McLellan, 2019 ; Stasiak and Stehle, 2020 ). The novel coronavirus SARS-CoV-2 binds the cellular receptor Angiotensin-converting enzyme 2 (ACE2) to cause coronavirus disease 2019 (COVID-19) ( Yan et al., 2020 ).…”

Adenovirus and the Cornea: More Than Meets the Eye

“…Subsequent work showed that some but not all of the EKC-associated HAdVs bind to sialic acid-expressing cell surface glycans [ 85 ], and that various multivalent sialic acid constructs could block binding [ 84 , 86 , 87 , 88 , 89 , 90 , 91 ]. Sites on the fiber knob that bind to the various potential adenovirus receptors have been mapped in exquisitely detailed structural studies [ 92 ]. Binding is not only specific to HAdV species [ 76 ], but also differs within HAdV species [ 65 , 77 , 93 , 94 ].…”

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