High-resolution comparative atomic structures of two Giardiavirus prototypes infectingG. duodenalisparasite

Abstract

AbstractGiardia lamblia virus(GLV) is a non-enveloped icosahedral dsRNA virus and an endosymbiont virus infecting the zoonotic protozoan parasiteGiardia duodenalis(syn.G. lamblia, G. intestinalis), a pathogen of mammals, including humans. Elucidating the transmission mechanism of GLV is crucial to an in-depth understanding of the virulence of the virus inG. duodenalis. GLV belongs to the familyTotiviridae,which infects yeast and protozoa intracellularly; however, it also transmits extracellularly, similar to phylogenetically distantly related toti-like viruses that infect multicellular hosts. The GLV capsid structure is extensively involved in the longstanding discussion concerning the acquisition of extracellular transmission inTotiviridaeand toti-like viruses. Hence, this study constructed the first high-resolution comparative atomic models of two GLV strains, namely GLV-HP and GLV-CAT, which showed different intracellular localization and virulence phenotypes, using cryo-EM single-particle analysis. The atomic models of the GLV capsids presented swapped C-terminal extensions, extra surface loops, and a lack of cap-snatching pockets, similar to those of toti-like viruses. However, their open pores and lack of the extra crown protein (CrP) resemble those of other yeast and protozoanTotiviridaeviruses, demonstrating the essential structures for acquiring extracellular cell-to-cell transmission. The intensive structural comparison between GLV-HP and GLV-CAT indicates the first evidence of critical structural motifs for the transmission and virulence of GLV inG. duodenalis.