Relationship between viral host range and use of alternative receptors for viral entry.

The distribution of the number of host species per virus is shown for viruses for which there is only one known protein receptor functionally sufficient for entry, versus those with alternative receptors. Virus-host associations were obtained from a previous publication (see text).</p

Relevant features identified by the GBM.

Gain represents the relative contribution of each variable to the model prediction. Cover indicates the relative number of observations that are related to a given variable. (XLSX)</p

Numbers of distinct host factors, viruses, and virus-host interactions collected in this study as well as previous publications and databases.

Numbers of distinct host factors, viruses, and virus-host interactions collected in this study as well as previous publications and databases.</p

Scores obtained from the GBM.

The gene symbol, assigned score (probability of being a receptor), and whether the corresponding protein is a known receptor are indicated. (XLSX)</p

Virus receptor discovery trends.

A. Venn diagram showing the number of virus-receptor interactions in three databases combined (ViralZone, KEGG, VTHunter), two previous reviews or meta-analyses (see text), and the search performed in this study. Areas are proportional to the number of interactions described, and numbers indicate the total number of pairs from each source. See Tables 1 and S1 for details. B. Cumulated numbers of distinct virus-receptor interactions, viruses, and host factors discovered per year.</p

Research effort versus the known number of host proteins used as receptors for different viral families.

Data points correspond to individual viruses. Those corresponding to the indicated family are shown in color (blue for non-enveloped viruses; yellow for enveloped viruses), and grey points correspond to all other viruses. The colored and grey dashed lines show the GLM prediction obtained specifically for the family and all viruses, respectively. Only families with at least 5 viral species in the dataset were considered. (TIF)</p

Variation in the number of known receptors across viruses.

A. Relationship between research effort, measured the number of PubMed records and the number of different proteins used as receptors for each virus. The dashed line shows the expected number of receptors obtained from a GLM (null model), and dotted lines correspond to 95% confidence intervals. B. Known receptors versus the expected number under the null model shown in panel A. The dashed line indicates no deviation from the model, and the dotted lines the 95% confidence interval. Viruses shown in yellow exceed the upper limit of the confidence interval and have more than 10 known receptors. Viruses shown in blue fall below the lower limit of the confidence interval, and their expected number of receptors according to the model is higher than five. CVB: Coxsackievirus B (enterovirus B); DENV: dengue virus; EBOV: Zaire ebolavirus; HCV: hepatitis C virus (hepacivirus C); HSV-1: herpes simplex virus 1 (human alphaherpesvirus 1); PV: poliovirus (enterovirus C); SINV: Sindbis virus; WNV: West Nile virus.</p

Virus-receptor interactions classified according to the nature and role of the host factors involved, showing differences between enveloped and non-enveloped viruses.

Virus-receptor interactions classified according to the nature and role of the host factors involved, showing differences between enveloped and non-enveloped viruses.</p

Workflow for the manual and automatic text-mining searches.

A starting list of 6034 mammal viruses was used to obtain, which were then reviewed using both manual and PubmedKB-based automated strategies. The resulting virus-receptor pairs were combined with known databases and manually curated (see text for full description). M, manual strategy; PKB, PubmedKB strategy. (TIF)</p

Roles of known receptors according to viral family.

Only families with at least 10 known virus-host interactions are represented. Families of enveloped and non-enveloped viruses are shown, and within each group, families are sorted by the fraction of known receptors that are sufficient for viral entry (main plus alternative receptors). (TIF)</p