Virus–Receptor Interactions: The Key to Cellular Invasion

Abstract

Virus-receptor interactions play a key regulatory role in viral host range, tissue tropism, and viral pathogenesis. Viruses utilize elegant strategies to attach to one or multiple receptors, overcome the plasma membrane barrier, enter, and access the necessary host cell machinery. The viral attachment protein can be viewed as the "key" that unlocks host cells by interacting with the "lock"-the receptor-on the cell surface, and these lock-and-key interactions are critical for viruses to successfully invade host cells. Many common themes have emerged in virus-receptor utilization within and across virus families demonstrating that viruses often target particular classes of molecules in order to mediate these events. Common viral receptors include sialylated glycans, cell adhesion molecules such as immunoglobulin superfamily members and integrins, and phosphatidylserine receptors. The redundancy in receptor usage suggests that viruses target particular receptors or "common locks" to take advantage of their cellular function and also suggests evolutionary conservation. Due to the importance of initial virus interactions with host cells in viral pathogenesis and the redundancy in viral receptor usage, exploitation of these strategies would be an attractive target for new antiviral therapeutics.

Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates

“…Furthermore, we cannot exclude the possibility that infection in any species occurs via another cellular receptor (for a review see ref. 34 ), as shown for other betacoronaviruses ( 35 ), or lower-affinity interactions with ACE2 as proposed for SARS-CoV ( 2 ). Nonetheless, our predictions provide a useful starting point for the selection of appropriate animal models for COVID-19 research and identification of species that may be at risk for human-to-animal or animal-to-animal transmissions of SARS-CoV-2.…”

Genetic Manipulation of Human Intestinal Enteroids Demonstrates the Necessity of a Functional Fucosyltransferase 2 Gene for Secretor-Dependent Human Norovirus Infection

“…It is likely that initial binding of secretor-dependent HuNoVs to HIEs is regulated by fucosylation, with the attachment factors being fucosylated. However, it is unclear whether the fucosylated molecules serve only as the initial attachment factor that then facilitates interaction with a virus-specific receptor or whether the fucosylated molecules function as a virus receptor themselves; examples of both mechanisms have been described previously with nonfucosylated glycans (22). For example, reovirus binding to its proteinaceous JAM-A receptor is enhanced by initial binding to sialic acid residues (23), while human coronaviruses OC43 and HKU1 bind to 9-O-acetylated sialic acid receptors (24) and influenza viruses bind to terminal sialic acid receptors (25).…”

Saliva: potential diagnostic value and transmission of 2019-nCoV

“…In the cycle of infection for most virus, the first step is to attach to the surface and recognize cell surface receptor of the host cell for invasion. 15,16 With similar external subdomain of receptor-binding domain (RBD), 2019-nCoV spike share same host-cell receptorangiotensin-converting enzyme II (ACE2)-with SARS-CoV spike, but in a higher affinity than SARS-CoV spike. [17][18][19][20][21] In another word, cells expressing cell surface receptor ACE2 are susceptible to 2019-nCoV, similar to SARS-CoV.…”