Lessons learned from adenovirus (1970–2019)

Abstract

Animal viruses are well recognized for their ability to uncover fundamental cell and molecular processes, and adenovirus certainly provides a prime example. This review illustrates the lessons learned from studying adenovirus over the past five decades. We take a look back at the key studies of adenovirus structure and biophysical properties, which revealed the mechanisms of adenovirus association with antibody, cell receptor, and immune molecules that regulate infection. In addition, we discuss the critical contribution of studies of adenovirus gene expression to elucidation of fundamental reactions in pre‐mRNA processing and its regulation. Other pioneering studies furnished the first examples of protein‐primed initiation of DNA synthesis and viral small RNAs. As a nonenveloped virus, adenoviruses have furnished insights into the modes of virus attachment, entry, and penetration of host cells, and we discuss the diversity of cell receptors that support these processes, as well as membrane penetration. As a result of these extensive studies, adenovirus vectors were among the first to be developed for therapeutic applications. We highlight some of the early (unsuccessful) trials and the lessons learned from them.

High-Throughput Cloning and Characterization of Emerging Adenovirus Types 70, 73, 74, and 75

“…Adenoviruses are medium-sized (70–100 nm in diameter), non-enveloped icosahedral viruses composed of double-stranded linear DNA genome with an average length of 26–45 kb [ 1 ]. In humans more than 100 adenovirus types have been identified and classified into seven species (A to G) based on hemagglutination properties, oncogenicity in rodents, DNA homology, and genomic organization [ 2 , 3 ]. Human adenoviruses (HAdVs) cause significant numbers of respiratory, ocular, and gastrointestinal diseases and incidences of severe diseases caused by adenoviruses most occur in immunocompromised individuals or toddlers [ 4 , 5 , 6 ].…”

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 .…”

“…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 . The latter is mediated by protein VI with an amphipathic helix interacting with sphingolipids 72,73,74,75,76,77,78,79 .…”

Synthesis, Structure, and Function of Human Adenovirus Small Non-Coding RNAs

“…In addition to their pathogenicity, HAdVs have gained a lot of attention as the experimental tools to study various molecular biology mechanisms and as the robust therapeutic tools suitable for disease treatment and prevention. Extensive cell biology and biochemistry studies using HAdV infections or HAdV-encoded proteins/RNAs have revealed the molecular mechanisms involved in anti-viral immune responses, virus uptake, mRNA processing, DNA replication and protein degradation [ 3 ]. This basic molecular virology knowledge has been instrumental to design genetically modified adenoviruses for therapeutic purposes.…”

“…However, most of the functional studies have been carried out using the genetically almost identical virus types 2 and 5 (HAdV-2 and HAdV-5) [ 7 ]. HAdVs can infect a variety of cell types and they typically establish a lytic infection causing fast and efficient recipient cell lysis [ 3 ]. In addition to the relatively well-characterized lytic infection, some virus types, such as HAdV-2 and HAdV-5, can also establish enigmatic long-term persistent infections in B and T cells [ 8 , 9 ].…”