Special Issue: Virus Receptors and Viral Tropism

Cell surface receptors play a key role in a virus’ ability to recognize and invade cells and tissues, which basically defines viral pathogenicity [...]

Recent Advances in PRRS Virus Receptors and the Targeting of Receptor–Ligand for Control

Cellular receptors play a critical role in viral infection. At least seven cellular molecules have been identified as putative viral entry mediators for porcine reproductive and respiratory syndrome virus (PRRSV). Accumulating data indicate that among these candidates, CD163, a cysteine-rich scavenger receptor on macrophages, is the major receptor for PRRSV. This review discusses the recent advances and understanding of the entry of PRRSV into cells, viral pathogenesis in CD163 gene-edited swine, and CD163 as a potential target of receptor–ligand for the control of PRRS.

Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity

The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.

Vertical Transmission of SARS-CoV-2 (COVID-19): Are Hypotheses More than Evidences?

In spite of the increasing, accumulating knowledge on the novel pandemic coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), questions on the coronavirus disease-2019 (COVID-19) infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending and have not been addressed so far. SARS-CoV-2, a RNA single-stranded virus, has been detected in the amniotic fluid, in the cord blood and in the placentas of the infected women. In the light of these findings, the theoretical risk of intrauterine infection for fetuses, or of peripartum infection occurring during delivery for neonates, has a biological plausibility. The extent of this putative risk might, however, vary during the different stages of pregnancy, owing to several variables (physiological modifications of the placenta, virus receptors' expression, or delivery route). This brief review provides an overview of the current evidence in this area. Further data, based on national and international multicenter registries, are needed not only to clearly assess the extent of the risk for vertical transmission, but also to ultimately establish solid guidelines and consistent recommendations. Key Points

Prediction of the receptorome for the human-infecting virome

The virus receptors are key for the viral infection of host cells. Identification of the virus receptors is still challenging at present. Our previous study has shown that human virus receptor proteins have some unique features including high N-glycosylation level, high number of interaction partners and high expression level. Here, a random-forest model was built to identify human virus receptorome from human cell membrane proteins with an accepted accuracy based on the combination of the unique features of human virus receptors and protein sequences. A total of 1380 human cell membrane proteins were predicted to constitute the receptorome of the human-infecting virome. In addition, the combination of the random-forest model with protein-protein interactions between human and viruses predicted in previous studies enabled further prediction of the receptors for 693 human-infecting viruses, such as the Enterovirus, Norovirus and West Nile virus. As far as we know, this study is the first attempt to predict the receptorome for the human-infecting virome and would greatly facilitate the identification of the receptors for viruses.

Phage protein receptors have multiple interaction partners and high expressions

Motivation Receptors on host cells play a critical role in viral infection. How phages select receptors is still unknown. Results Here, we manually curated a high-quality database named phageReceptor, including 427 pairs of phage–host receptor interactions, 341 unique viral species or sub-species and 69 bacterial species. Sugars and proteins were most widely used by phages as receptors. The receptor usage of phages in Gram-positive bacteria was different from that in Gram-negative bacteria. Most protein receptors were located on the outer membrane. The phage protein receptors (PPRs) were highly diverse in their structures, and had little sequence identity and no common protein domain with mammalian virus receptors. Further functional characterization of PPRs in Escherichia coli showed that they had larger node degrees and betweennesses in the protein–protein interaction network, and higher expression levels, than other outer membrane proteins, plasma membrane proteins or other intracellular proteins. These findings were consistent with what observed for mammalian virus receptors reported in previous studies, suggesting that viral protein receptors tend to have multiple interaction partners and high expressions. The study deepens our understanding of virus–host interactions. Availability and implementation phageReceptor is publicly available from: http://www.computationalbiology.cn/phageReceptor/index.html. Supplementary information Supplementary data are available at Bioinformatics online.

Advances in high-throughput methods for the identification of virus receptors

Viruses have evolved many mechanisms to invade host cells and establish successful infections. The interaction between viral attachment proteins and host cell receptors is the first and decisive step in establishing such infections, initiating virus entry into the host cells. Therefore, the identification of host receptors is fundamental in understanding pathogenesis and tissue tropism. Furthermore, receptor identification can inform the development of antivirals, vaccines, and diagnostic technologies, which have a substantial impact on human health. Nevertheless, due to the complex nature of virus entry, the redundancy in receptor usage, and the limitations in current identification methods, many host receptors remain elusive. Recent advances in targeted gene perturbation, high-throughput screening, and mass spectrometry have facilitated the discovery of virus receptors in recent years. In this review, we compare the current methods used within the field to identify virus receptors, focussing on genomic- and interactome-based approaches.

From phages to mammalian viruses: viral receptors play a central role in protein-protein interaction network

MotivationReceptors on host cells play a critical role in viral infection. How phages select receptors is still unknown.ResultsHere, we manually curated a high-quality database named phageReceptor, including 355 pairs of phage-host receptor interactions, 280 unique viral species or sub-species and 64 bacterial species. Sugars and proteins were most widely used by phages as receptors. The receptor usage of phages in Gram-positive bacteria was different from that in Gram-negative bacteria. Most protein receptors were located on the outer membrane. The protein receptors were highly diverse in their structures, and had little homology with mammalian virus receptors. Further functional characterization of phage protein receptors in Escherichia coli showed that they had larger node degrees and betweennesses in the protein-protein interaction (PPI) network, and higher expression levels, than other outer membrane proteins, plasma membrane proteins, or other intracellular proteins. These findings were consistent with what observed for mammalian virus receptors, suggesting that viral protein receptors play a central role in the host’s PPI network. The study deepens our understanding of virus-host interactions.AvailabilityThe database of phageReceptor is publicly accessible at http://www.computationalbiology.cn/viralRecepetor/index.html.