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. 2022 Dec 20;41(12):111754.
doi: 10.1016/j.celrep.2022.111754.

Comprehensive profiling of antibody responses to the human anellome using programmable phage display

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Free article

Comprehensive profiling of antibody responses to the human anellome using programmable phage display

Thiagarajan Venkataraman et al. Cell Rep. .
Free article

Abstract

Anelloviruses represent a major constituent of the commensal human virome; however, little is known about their immunobiology. Here, we present "AnelloScan," a T7 phage library representing the open reading frame 1 (ORF1), ORF2, ORF3, and torque teno virus (TTV)-derived apoptosis-inducing protein (TAIP) sequences of more than 800 human anelloviruses and profile the antibody reactivities of serum samples from a cross-sectional cohort of 156 subjects by using phage-immunoprecipitation sequencing (PhIP-Seq). A majority of anellovirus peptides are not reactive in any of the subjects tested (n = ∼28,000; ∼85% of the library). Antibody-reactive peptides are largely restricted to the C-terminal region of the capsid protein ORF1. Moreover, using a longitudinal cohort of matched blood-transfusion donors and recipients, we find that most transmitted anelloviruses do not elicit a detectable antibody reactivity in the recipient and that the remainder elicit delayed responses appearing ∼100-150 days after transfusion.

Keywords: AnelloScan; CP: Microbiology; PhIP-seq; TTV; VirScan; anelloviridae; anellovirus; antibodies; torque teno virus; transfusion.

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Conflict of interest statement

Declaration of interests H.S., C.A.A., S.M.J., A.B., T.D., D.M.N., S.D., and N.L.Y. are employees of and hold equity interests in Ring Therapeutics. V.M. is an employee of and holds equity interests in Flagship Pioneering, which also holds an equity interest in Ring Therapeutics. H.B.L. is an inventor on an issued patent (US20160320406A) filed by Brigham and Women’s Hospital that covers the use of the VirScan technology; is a founder of ImmuneID, Portal Bioscience, and Alchemab; and is an advisor to TScan Therapeutics.

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