Biology subjects

Wells, H. L.

Publications and source records attributed to Wells, H. L..

4 recordsLinked to original sources

bioRxiv2026

From receptor binding to biogeography: Multi-scale prediction of filovirus hosts in bats

Forecasting zoonotic risk requires identifying which host species are biologically susceptible to infection, yet susceptibility is rarely predicted using frameworks that integrate molecular mechanisms with macroecology. Filoviruses, a diverse group of bat-associated viruses that include Ebola and Marburg viruses, illustrate this challenge: viral entry depends on interactions between viral glycoproteins and the host receptor NPC1, and host ecology and distribution determine opportunity of viral entry. Additionally, receptor sequence data used for informing viral entry are available for only a small fraction of bat species. Here, we extend virus-specific susceptibility prediction across the global diversity of bats by integrating experimentally measured and physicochemically inferred virus-receptor binding strengths with phylogenetic, ecological, and environmental data. Using boosted regression models trained on binding assay labels, we generate predictions of NPC1-mediated binding strength for more than 1,300 bat species. Predicted susceptibility is strongly structured by evolutionary relationships, with high binding concentrated in particular bat lineages, but is further differentiated within clades by morphology, life-history strategy, and environmental context. Strikingly, macroevolutionary structure alone recovers interaction patterns originally derived from amino acid-level physicochemistry, indicating that information about receptor-mediated compatibility is recoverable from host evolutionary history and ecological traits. Predicted high binding strength extends well beyond historically recognized outbreak regions, suggesting that the fundamental host range of filoviruses may be substantially broader than their currently realized distribution. By scaling receptor biology to global host diversity, this multi-scale framework expands mechanistic susceptibility forecasting beyond species with available molecular data and provides a generalizable approach for integrating molecular and ecological information in zoonotic prediction.

ecology↗

bioRxiv2026

Generation-Establishment Tradeoffs Shape the Temporal Window of Recombinant Evolution

Recent viral coinfection experiments show that recombinant genomes are generated readily and depend strongly on infection timing and order, yet only a small fraction give rise to persistent lineages. We develop a hybrid deterministic-stochastic framework that resolves this discrepancy by coupling density-dependent recombinant generation with stochastic establishment of rare lineages. The resulting hazard of successful lineage formation is generically non-monotonic, increasing with parental abundance through enhanced generation while decreasing under competitive suppression, and exhibits a unique interior maximum in parental-density space. As parental populations evolve, their trajectory across this hazard landscape defines a sharply localized temporal window of evolutionary opportunity. These results reveal a general principle: evolutionary success is determined not only by intrinsic fitness, but by when variants arise within a dynamically changing ecological context.

biophysics↗

bioRxiv2021

Taxonomic classification methods reveal a new subgenus in the paramyxovirus subfamily Orthoparamyxovirinae

As part of a broad One Health surveillance effort to detect novel viruses in wildlife and people, we report several paramyxoviruses sequenced primarily from bats during 2013 and 2014 in Brazil and Malaysia, including seven from which we recovered full-length genomes. Of these, six represent the first full-length paramyxovirus genomes sequenced from the Americas, including two sequences which are the first full-length bat morbillivirus genomes published to date. Our findings add to the vast number of viral sequences in public repositories that have been increasing considerably in recent years due to the rising accessibility of metagenomics. Taxonomic classification of these sequences in the absence of phenotypic data has been a significant challenge, particularly in the paramyxovirus subfamily Orthoparamyxovirinae, where the rate of discovery of novel sequences has been substantial. Using pairwise amino acid sequence classification (PASC), we describe a novel genus within this subfamily tentatively named Jeishaanvirus, which we propose should include as subgenera Jeilongvirus, Shaanvirus, and a novel South American subgenus Cadivirus. We also highlight inconsistencies in the classification of Tupaia virus and Mojiang virus using the same demarcation criteria and show that members of the proposed subgenus Shaanvirus are paraphyletic. Importantly, this study underscores the critical importance of sequence length in PASC analysis as well as the importance of biological characteristics such as genome organization in the taxonomic classification of viral sequences.

microbiology↗

bioRxiv2020

The evolutionary history of ACE2 usage within the coronavirus subgenus Sarbecovirus

SARS-CoV-1 and SARS-CoV-2 are not phylogenetically closely related; however, both use the ACE2 receptor in humans for cell entry. This is not a universal sarbecovirus trait; for example, many known sarbecoviruses related to SARS-CoV-1 have two deletions in the receptor binding domain of the spike protein that render them incapable of using human ACE2. Here, we report three sequences of a novel sarbecovirus from Rwanda and Uganda which are phylogenetically intermediate to SARS-CoV-1 and SARS-CoV-2 and demonstrate via in vitro studies that they are also unable to utilize human ACE2. Furthermore, we show that the observed pattern of ACE2 usage among sarbecoviruses is best explained by recombination not of SARS-CoV-2, but of SARS-CoV-1 and its relatives. We show that the lineage that includes SARS-CoV-2 is most likely the ancestral ACE2-using lineage, and that recombination with at least one virus from this group conferred ACE2 usage to the lineage including SARS-CoV-1 at some time in the past. We argue that alternative scenarios such as convergent evolution are much less parsimonious; we show that biogeography and patterns of host tropism support the plausibility of a recombination scenario; and we propose a competitive release hypothesis to explain how this recombination event could have occurred and why it is evolutionarily advantageous. The findings provide important insights into the natural history of ACE2 usage for both SARS-CoV-1 and SARS-CoV-2, and a greater understanding of the evolutionary mechanisms that shape zoonotic potential of coronaviruses. This study also underscores the need for increased surveillance for sarbecoviruses in southwestern China, where most ACE2-using viruses have been found to date, as well as other regions such as Africa, where these viruses have only recently been discovered.

evolutionary biology↗