High-resolution comparative atomic structures of two Giardiavirus prototypes infecting G. duodenalis parasite

• Published in: PLoS pathogens 2024-04, Vol.20 (4), p.e1012140-e1012140
• Main Authors: Wang, Han, Marucci, Gianluca, Munke, Anna, Hassan, Mohammad Maruf, Lalle, Marco, Okamoto, Kenta
• Format: Article
• Language: English
• Subjects: Analysis; Biology and Life Sciences; Capsids; Care and treatment; Diagnosis; Disease transmission; Double-stranded RNA; Electron microscopy; Giardia; Giardia lamblia; Giardiasis; High resolution; Localization; Medicine and Health Sciences; Parasites; Phenotypes; Phylogeny; Prevention; Protozoa; Research and Analysis Methods; Risk factors; Totiviridae; Virulence; Virulence (Microbiology); Viruses; Yeast; Yeasts
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1012140

The Giardia lamblia virus (GLV) is a non-enveloped icosahedral dsRNA and endosymbiont virus that infects the zoonotic protozoan parasite Giardia duodenalis (syn. G. lamblia, G. intestinalis), which is a pathogen of mammals, including humans. Elucidating the transmission mechanism of GLV is crucial for gaining an in-depth understanding of the virulence of the virus in G. duodenalis. GLV belongs to the family Totiviridae, which infects yeast and protozoa intracellularly; however, it also transmits extracellularly, similar to the phylogenetically, distantly related toti-like viruses that infect multicellular hosts. The GLV capsid structure is extensively involved in the longstanding discussion concerning extracellular transmission in Totiviridae and 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 cryogenic electron microscopy 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 absence of the extra crown protein resemble those of other yeast and protozoan Totiviridae viruses, demonstrating the essential structures for extracellular cell-to-cell transmission. The structural comparison between GLV-HP and GLV-CAT indicates the first evidence of critical structural motifs for the transmission and virulence of GLV in G. duodenalis.