Adenoviruses – Infection, pathogenesis and therapy

Abstract

Both well-known and emerging viruses increasingly affect humans and cause disease, sometimes with devastating impact on society. The viruses present in the biosphere are the top predators in the life chain, virtually without enemies, except perhaps the immune system, and harsh environmental physicochemical conditions restricting their dissemination. We know a lot about viruses, but do we know enough? This series of reviews is dedicated to adenoviruses (AdVs), a family of nonenveloped DNA viruses occurring in vertebrates, including humans. AdVs have been the focus of intense research for more than 67 years. Besides causing disease, they have immensely contributed to the advance of life sciences and medicine over the past decades. Recently, AdVs have been widely used as vehicles in gene therapy and vaccination. They continue to provide fundamental insights into virus-host interactions in cells, tissues and organisms, as well as systems and metabolic networks. This special issue of FEBS Letters presents a unique collection of 23 state-of-theart review articles by leading adenovirologists. In this prelude, I present the chapters, which provide a solid basis for further exploring the rich heritage in adenovirus molecular cell biology, structural biology, genetics, immunology, gene therapy and epidemiology. I conclude with an essential discussion of six blind spots in adenovirology.Adenoviruses (AdVs) are nonenveloped, doublestranded DNA viruses of vertebrates. They are abundant in fish, amphibia, reptilia, birds and mammals, including humans. Currently, about 110 human adenovirus (HAdV) types and genotypes are known and classified into seven species (A-G). AdVs infect the respiratory organs, the eyes, the kidney, the gastrointestinal tract and blood cells. On a population scale, AdVs emerge unpredictable, and can cause human epidemics.The structure of the virion is related to phages of eubacteria and archaea, and is part of an evolutionary lineage comprising the internal membrane-bearing PRD1 phage of the tectiviridae infecting Gram-negative bacteria, paramecium bursaria chlorella virus infecting green algae, sulfolobus turreted icosahedral virus infecting archaea, as well as vaccinia virus, an attenuated form of the cowpox disease virus, related to variola virus causing small pox [1][2][3][4][5]. Both AdVs

Microscopy deep learning predicts virus infections and reveals mechanics of lytic-infected cells

“…For viruses replicating in the nucleus, a key step is to transfer the viral genome to the cytoplasm. For example, human immunodeficiency virus or influenza virus use the nuclear export machineries to transport their unpackaged genomes from the nucleus to the cytoplasm ( Boulo et al., 2007 ; Cullen, 2003 ), whereas AdVs, parvoviruses, or polyomaviruses package their genome into a protein capsid and induce the rupture of the NE ( Daniels et al., 2007 ; Greber, 2020 ; Majumder et al., 2018 ; Puvion-Dutilleul et al., 1998 ; Suzuki et al., 2010 ; Tollefson et al., 1996b ). Other capsids, for instance those from herpesviruses and baculoviruses, egress from the nucleus by engaging non-disruptive processes, including budding and fusion in the nuclear membranes ( Bigalke and Heldwein, 2016 ; Blissard and Theilmann, 2018 ; Wang et al., 2018 ; Zeev-Ben-Mordehai et al., 2015 ), although herpesviruses were also reported to rupture the NE, or dilatate nuclear pores ( Grimm et al., 2012 ; Klupp et al., 2011 ; Maric et al., 2014 ; Wild et al., 2019 ).…”

“…Poorly controlled HSV-1 can give rise to encephalitis, conjunctivitis, Bell's palsy, eczema, or genital skin lesion. AdVs, in turn, infect the respiratory, ocular and digestive tracts, as well as blood cells and persist in lymphoid cells of human intestines and tonsils ( Greber, 2020 ; Greber et al., 2013 ; Greber and Flatt, 2019 ; Lion, 2014 ). Upon immunosuppression, they spread to intestinal epithelial cells by unknown pathways and cause severe morbidity and mortality ( Kosulin et al., 2016 ).…”

The E3 ubiquitin ligase Mind bomb 1 enhances nuclear import of viral DNA by inactivating a virion linchpin protein that suppresses exposure of virion pathogen-associated molecular patterns

“…Understanding how cells control virion stability is key to pathology and advances the field of synthetic virology, for example for the development of customized gene delivery vehicles and vaccines. Human AdVs and their interactions with cells are a highly advanced model of virus-host interactions at all levels, ranging from single cell infection, immunity, persistent and acute human disease to therapy and vaccination 35,56,68,69 . Human AdV particles are composed of major and minor capsid proteins conferring structural and accessory functions, such as DNA confinement, particle stability or membrane rupture 68,70,71 .…”

“…Additional cues for uncoating are ubiquitination in the case of influenza virus, vaccinia virus, dengue virus, and AdV 29,30,31,32 . AdVs have a long history as vectors in gene therapy and vaccination, including coronavirus vaccine development, currently in late stages of clinical trials 33,34,35,36 . Human AdVs infect the gastrointestinal and respiratory tract as well as eyes 37,38,39 .…”

On-chip transporting arresting and characterizing individual nano-objects in biological ionic liquids

“…They are common pathogens in humans and animals. The ability to control and study them individually can help in the challenging determination of their infection pathway (58)(59)(60).…”