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A viral ubiquitination switch attenuates innate immunity and triggers nuclear import of virion DNA and infection.

Science advances (2021-12-18)
Michael Bauer, Alfonso Gomez-Gonzalez, Maarit Suomalainen, Nicolas Schilling, Silvio Hemmi, Urs F Greber
ABSTRACT

Antiviral defense and virus exclusion from the cell nucleus restrict foreign nucleic acid influx and infection. How the genomes of DNA viruses evade cytosolic pattern recognition and cross the nuclear envelope is incompletely understood. Here, we show that the virion protein V of adenovirus functions as a linchpin between the genome and the capsid, thereby securing particle integrity. Absence of protein V destabilizes cytoplasmic particles and promotes premature genome release, raising cytokine levels through the DNA sensor cGAS. Non-ubiquitinable V yields stable virions, genome misdelivery to the cytoplasm, and increased cytokine levels. In contrast, normal protein V is ubiquitinated at the nuclear pore complex, dissociates from the virion depending on the E3 ubiquitin ligase Mib1 and the proteasome, and allows genome delivery into the nucleus for infection. Our data uncover previously unknown cellular and viral mechanisms of viral DNA nuclear import in pathogenesis, vaccination, gene therapy, and synthetic biology.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Mouse MCP-1 / CCL2 ELISA Kit, for serum, plasma and cell culture supernatant
Sigma-Aldrich
Mouse RANTES / CCL5 ELISA Kit, for serum, plasma and cell culture supernatant
Sigma-Aldrich
Anti-E1A (Ad2/Ad5) Antibody, clone M73, clone M73, Upstate®, from mouse