Adenovirus entry: Stability, uncoating, and nuclear import. Issue 4 (26th April 2022)

• Record Type: Journal Article
• Authors: Greber, Urs F.; Suomalainen, Maarit
• Is Part Of: Molecular microbiology. Volume 118:Issue 4(2022)
• Page Start: 309
• Page End: 320
• Publication Date: 2022-04-26
• Subjects: DNA nuclear transport -- Mind bomb 1 (MIB1) E3 ubiquitin ligase -- nuclear pore complex (NPC) -- ubiquitin proteasome system -- virus entry and disassembly; Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14909
• Languages: English
• ISSNs: 0950-382X

Abstract

Abstract: Adenoviruses (AdVs) are widespread in vertebrates. They infect the respiratory and gastrointestinal tracts, the eyes, heart, liver, and kidney, and are lethal to immunosuppressed people. Mastadenoviruses infecting mammals comprise several hundred different types, and many specifically infect humans. Human adenoviruses are the most widely used vectors in clinical applications, including cancer treatment and COVID‐19 vaccination. AdV vectors are physically and genetically stable and generally safe in humans. The particles have an icosahedral coat and a nucleoprotein core with a DNA genome. We describe the concept of AdV cell entry and highlight recent advances in cytoplasmic transport, uncoating, and nuclear import of the viral DNA. We highlight a recently discovered "linchpin" function of the virion protein V ensuring cytoplasmic particle stability, which is relaxed at the nuclear pore complex by cues from the E3 ubiquitin ligase Mind bomb 1 (MIB1) and the proteasome triggering disruption. Capsid disruption by kinesin motor proteins and microtubules exposes the linchpin and renders protein V a target for MIB1 ubiquitination, which dissociates V from viral DNA and enhances DNA nuclear import. These advances uncover mechanisms controlling capsid stability and premature uncoating and provide insight into nuclear transport of nucleic acids. Abstract : Viruses invade organisms and cells, cause disease, persist for a lifetime, or are eliminated by host defense. Viral vectors are beneficial to clinical therapy or preventive vaccination. Adenoviruses are widespread human pathogens and the most widely used vectors in gene therapy. Here we provide an updated coherent concept for nuclear entry of a human virus, a key process in infection and immunity.