Capsid opening enables genome release of iflaviruses

Abstract

The family Iflaviridae includes economically important viruses of the western honeybee such as deformed wing virus, slow bee paralysis virus, and sacbrood virus. Iflaviruses have nonenveloped virions and capsids organized with icosahedral symmetry. The genome release of iflaviruses can be induced in vitro by exposure to acidic pH, implying that they enter cells by endocytosis. Genome release intermediates of iflaviruses have not been structurally characterized. Here, we show that conformational changes and expansion of iflavirus RNA genomes, which are induced by acidic pH, trigger the opening of iflavirus particles. Capsids of slow bee paralysis virus and sacbrood virus crack into pieces. In contrast, capsids of deformed wing virus are more flexible and open like flowers to release their genomes. The large openings in iflavirus particles enable the fast exit of genomes from capsids, which decreases the probability of genome degradation by the RNases present in endosomes.

Cold case: The disappearance of Egypt bee virus, a fourth distinct master strain of deformed wing virus linked to honeybee mortality in 1970’s Egypt

“…Although DWV can be detected in a wide range of insects, this is usually a secondary transmission in relation to a current, or historical, presence of infected Apis colonies in the area. The structural instability of the DWV particle in isolation [ 15 , 65 ] precludes extensive viability and persistence outside the host tissues, such as in stored foods or the external environment. It also means that all the major DWV transmission routes involve immediate, close, and direct transfer of inoculum between tissues or through secretions [ 14 , 72 ], which consequently requires a strong continuous presence of living hosts in close permanent contact with each other.…”

How Influenza Virus Uses Host Cell Pathways during Uncoating

“…Histone deacetylase 6 (HDAC6), epidermal growth factor receptor pathway substrate 8 (EPS8), transportin-1 (TRN-1 or TNPO1) have all been shown to be involved in the IAV core uncoating [ 102 , 103 , 104 ] and their role for other viruses begins to be examined. Catalyzing the capsid opening for a fast genome release may decrease the probability of the virus genetic material being degraded by cellular RNases as has been shown for iflaviruses, positive-strand RNA viruses from the family Iflaviridae (order Picornavirales) [ 105 ]. After release of the viral RNPs into the cytosol in the proximity of the cell nucleus, the vRNPs are imported into the nucleus through nuclear pore complexes using the nucleoprotein (NP) nuclear localization sequence (NLS) motifs and the importin α/β-dependent nuclear import pathway.…”

Cargo Release from Nonenveloped Viruses and Virus-like Nanoparticles: Capsid Rupture or Pore Formation

“…[10][11][12][13]16 Consequently, the attraction between pentamers of capsid proteins (stable building units of capsids) decreases, which enables the subsequent genome release. 7,8 The mechanism of genome release from picornaviruses has long been the subject of speculation. 10,11,18−24 It has been proposed that the pores on twofold, 10,11,19−23 threefold, 24 and fivefold 25−28 axes of symmetry serve as channels for the release of viral genomes.…”

“…32 Recently, picornavirus capsids with missing pentamers of capsid proteins were observed. [7][8][9]33 Consequently, a different pathway of genome release was described, in which capsids cracked open, and the genome was rapidly released. 7−9 Due to the fast dynamics and the stochastic nature of the release process, it is challenging to experimentally obtain molecular details of transient intermediates.…”