Applications of VirScan to broad serological profiling of bat reservoirs for emerging zoonoses

Bats host an unusually large number of viruses that can spill over into humans and cause severe disease — Hendra and Nipah henipaviruses, Marburg filovirus, rabies lyssavirus, and many coronaviruses among them — yet bats themselves rarely show clinical illness from these infections. Surveying which viruses any given bat population has been exposed to is hard: viral shedding is transient, traditional ELISA and virus-neutralization assays test only one antigen at a time, and field capture is logistically difficult.

This paper introduces a different approach. The authors took serum from two bat species — semi-captive Australian black flying foxes (Pteropus alecto) and captive Singaporean cave nectar bats (Eonycteris spelaea) — and ran each sample through the VirScan PhIP-Seq library, a bacteriophage-displayed collection of 56-mer peptides covering more than 200 viral species and 1,000 strains across the entire known human virome. By measuring which peptides each bat’s antibodies bound, they recovered a per-bat fingerprint of past viral exposures, then deconvoluted those fingerprints with the AVARDA algorithm to assign exposures to specific viral genera.

Despite the library being human-designed, the assay surfaced biologically plausible exposure histories: 57 viral genera in P. alecto and 9 in E. spelaea, including expected zoonotic groups. Pre-pandemic biosurveillance gains a virome-scale lever: a single PhIP-Seq run against the full human virome turns banked serum aliquots into hypothesis-free spillover-risk readouts, generalizable beyond Homo sapiens to mammalian reservoirs across One Health programs.