Anellovirus Structure Reveals a Mechanism for Immune Evasion

The significant impact of the human virome on human physiology is beginning to emerge thanks to modern sequencing methods and bioinformatic tools[1][1]. Anelloviruses, the principal constituent of the commensal human virome, are universally acquired in infancy and found throughout the body[2][2],[3][3],[4][4]. Since the discovery of the original torque teno virus in 1997[5][5], three genera of the Anelloviridae family, each extremely diverse genetically, have been found in humans. These viruses elicit weak immune responses that permit multiple strains to co-exist and persist for years in a typical individual[6][6]. However, because they do not cause disease[7][7] and due to the lack of an in vitro culture system, anelloviruses remain poorly understood[8][8],[9][9]. Basic features of the virus, such as the identity of its structural protein, have been unclear until now. Here, we describe the first structure of an anellovirus particle, which includes a jelly roll domain that forms a 60-mer icosahedral particle core from which spike domains extend to form a salient part of the particle surface. The spike domains come together around the 5-fold symmetry axes to form crown-like features. Relatively conserved patches of amino acids are near the base of the spike domain while a hypervariable region is at the apex. We propose that this structure renders the particle less susceptible to antibody neutralization by hiding vulnerable conserved epitopes while exposing highly diverse epitopes as immunological decoys, thereby contributing to the immune evasion properties of anelloviruses. This would contrast with viruses such as beak and feather disease virus, canine parvovirus or adeno-associated virus which lack such pronounced surface features. These results shed light on the structure of anelloviruses and provide a framework to understand their interactions with the immune system. ### Competing Interest Statement All authors are or were employed and hold equity interests in Ring Therapeutics. S.-H. L., N.C., S.D., and K.S. are the inventors on a patent application related to this work. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #ref-4 [5]: #ref-5 [6]: #ref-6 [7]: #ref-7 [8]: #ref-8 [9]: #ref-9