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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. Author summary: We determined the first atomic structure of a unique dsRNA virus known as the Giardia lamblia virus (GLV). The structure of GLV is important for two reasons. First, the GLV structure is the representative structure of a primitive group of viruses that infects unicellular parasites but has adapted an extracellular lifestyle. Hence, by comparing the structure of GLV with that of other dsRNA viruses, we could identify essential surface loop structures that have evolved to enable dsRNA viruses to infect their hosts extracellularly. Second, the GLV structure empowers us to formulate a strategy for engineering GLV, with a focus on its future therapeutic applications. G. duodenalis, a common zoonotic parasite, can infect both humans and domestic animals, often leading to severe diarrhea. Conventional anti-parasitic drugs are employed to treat G. duodenalis symptomatic infections; however, cases of refractories to these drugs are increasingly being reported. A new alternative approach gaining interest is virotherapy, which harnesses viruses that infect parasites to combat infections. An in-depth structural comparison between two GLV prototypes revealed significant structural mechanisms that potentially enhance the virulence of GLV for efficiently clearing Giardia parasites from infected patients. [ABSTRACT FROM AUTHOR]

Rosellinia necatrix megabirnavirus 1-W779 (RnMBV1) is a non-enveloped icosahedral double-stranded (ds)RNA virus that infects the ascomycete fungus Rosellinia necatrix, a causative agent that induces a lethal plant disease white root rot. Herein, we have first resolved the atomic structure of the RnMBV1 capsid at 3.2 Å resolution using cryo-electron microscopy (cryo-EM) single-particle analysis. Compared with other non-enveloped icosahedral dsRNA viruses, the RnMBV1 capsid protein structure exhibits an extra-long C-terminal arm and a surface protrusion domain. In addition, the previously unrecognized crown proteins are identified in a symmetry-expanded cryo-EM model and are present over the 3-fold axes. These exclusive structural features of the RnMBV1 capsid could have been acquired for playing essential roles in transmission and/or particle assembly of the megabirnaviruses. Our findings, therefore, will reinforce the understanding of how the structural and molecular machineries of the megabirnaviruses influence the virulence of the disease-related ascomycete fungus. Author summary: A fungal plant soil-borne pathogen, Rosellinia necatrix, which can cause devastating disease white root rot in many highly valued fruit trees, is difficult to be controlled with conventional approaches such as fungicide applications. Rosellinia necatrix megabirnavirus 1-W779 (RnMBV1) is a dsRNA virus isolated from the R. necatrix field strain, W779, and this virus can be a viro-control candidate to confer hypovirulence in its host R. necatrix. To make use of RnMBV1 in the white root rot disease control, more molecular and structural investigations will offer us more insights. Here, we have performed cryo-electron microscopy (cryo-EM) single-particle analysis, to obtain the first atomic models of RnMBV1 particles. Based on the atomic structures, we found unique both surface and interior features. In addition, we found a previously unidentified protein on the viral surface. These aforementioned structural features might play important roles in the viral life cycles, and will enable us to apply this fungal virus as a viro-control approach. [ABSTRACT FROM AUTHOR]