Murine adenoviruses: tools for studying adenovirus pathogenesis in a natural host

Hemmi, Silvio; Spindler, Katherine R.

doi:10.1002/1873-3468.13699

Cited by 14 publications

(13 citation statements)

References 115 publications

(179 reference statements)

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“…While more than 100 HAdV types have been described, there are only three MAdVs types known, MAdV-1 (M1), M2, and M3 [ 20 ]. M1/M2 were among the first nonprimate AdVs identified in the 1960s, isolated from common house mice [ 21 , 22 ], whereas M3 was isolated more recently from the striped field mouse [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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The RGD-binding integrins αvβ6 and αvβ8 are receptors for mouse adenovirus-1 and -3 infection

et al. 2021

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Mammalian adenoviruses (AdVs) comprise more than ~350 types including over 100 human (HAdVs) and just three mouse AdVs (MAdVs). While most HAdVs initiate infection by high affinity/avidity binding of their fiber knob (FK) protein to either coxsackievirus AdV receptor (CAR), CD46 or desmoglein (DSG)-2, MAdV-1 (M1) infection requires arginine-glycine-aspartate (RGD) binding integrins. To identify the receptors mediating MAdV infection we generated five novel reporter viruses for MAdV-1/-2/-3 (M1, M2, M3) transducing permissive murine (m) CMT-93 cells, but not B16 mouse melanoma cells expressing mCAR, human (h) CD46 or hDSG-2. Recombinant M1 or M3 FKs cross-blocked M1 and M3 but not M2 infections. Profiling of murine and human cells expressing RGD-binding integrins suggested that αvβ6 and αvβ8 heterodimers are associated with M1 and M3 infections. Ectopic expression of mβ6 in B16 cells strongly enhanced M1 and M3 binding, infection, and progeny production comparable with mαvβ6-positive CMT-93 cells, whereas mβ8 expressing cells were more permissive to M1 than M3. Anti-integrin antibodies potently blocked M1 and M3 binding and infection of CMT-93 cells and hαvβ8-positive M000216 cells. Soluble integrin αvβ6, and synthetic peptides containing the RGDLXXL sequence derived from FK-M1, FK-M3 and foot and mouth disease virus coat protein strongly interfered with M1/M3 infections, in agreement with high affinity interactions of FK-M1/FK-M3 with αvβ6/αvβ8, determined by surface plasmon resonance measurements. Molecular docking simulations of ternary complexes revealed a bent conformation of RGDLXXL-containing FK-M3 peptides on the subunit interface of αvβ6/β8, where the distal leucine residue dips into a hydrophobic pocket of β6/8, the arginine residue ionically engages αv aspartate215, and the aspartate residue coordinates a divalent cation in αvβ6/β8. Together, the RGDLXXL-bearing FKs are part of an essential mechanism for M1/M3 infection engaging murine and human αvβ6/8 integrins. These integrins are highly conserved in other mammals, and may favour cross-species virus transmission.

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Section: Introductionmentioning

confidence: 99%

“…Phylogenetically, M1 and M3 are more closely related to each other than to M2 [ 23 , 24 ]. MAdVs have characteristics in common with HAdVs and have been studied in acute and persistent infection using autologous models, with impact on vectorology in human gene therapy and vaccination [ 20 , 23 , 25 – 30 ].…”

Section: Introductionmentioning

confidence: 99%

The RGD-binding integrins αvβ6 and αvβ8 are receptors for mouse adenovirus-1 and -3 infection

et al. 2021

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“…Phase I studies have also been done in humans, but oral AdVs were only used in combination with intramuscular inactivated seasonal vaccine boost (47). To our knowledge, an animal model allowing study of replication competent AdV vaccine vectors in a permissive host, such as MAV-1 in mouse, has been studied to date (19,48). This work establishes an original and useful tool to better evaluate AdV vaccine platforms in vivo.…”

Section: Finally Recently Adv Vectors Have Emerged As Powerful Weapons To Oppose To the Sars-mentioning

confidence: 99%

A single oral immunization with a replication-competent adenovirus-vectored vaccine protects mice from influenza respiratory infection

Goffin¹,

Hemmi

Machiels³

et al. 2021

Preprint

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The development of effective and flexible vaccine platforms is a major public health challenge as recently highlighted by the COVID-19 pandemic. Adenoviruses (AdVs) are easy to produce and have a good safety and efficacy profile when administered orally as demonstrated by the long-term use of oral AdV 4 and 7 vaccines in the US military. These viruses therefore appear to be the ideal backbone for the development of oral replicative vector vaccines. However, research on these vaccines is limited by the ineffective replication of human AdVs in laboratory animals. The use of mouse AdV type 1 (MAV-1) in its natural host allows infection to be studied under replicative conditions. Here, we orally vaccinated mice with MAV-1 vectors expressing the full length or the headless hemagglutinin (HA) of influenza to assess the protection conferred against an intranasal challenge of influenza. We showed that while the headless HA vector did not generate a significant humoral or cellular immune response to influenza, a single oral immunisation with the full-length HA vaccine generated influenza-specific and neutralizing antibodies and completely protected the mice against clinical signs and viral replication.

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“…They highlight the similarities and remarkable differences between human and animal AdVs, their evolution and the potential threats to humans from zoonotic transmissions. Silvio Hemmi and Katherine Spindler review the current essential knowledge of murine AdVs, including mouse adenovirus type 1 (MAdV-1), but also MAdV-2 and MAdV-3, the last two belonging to the murine mastadenovirus species B and C, respectively [82]. The review focuses on MAdV-1, a member of the murine mastadenovirus species A, and describes the molecular genetics, virus life cycle, cell and tissue tropism.…”

Section: Animal Advsmentioning

confidence: 99%

Adenoviruses – Infection, pathogenesis and therapy

Greber

2020

FEBS Letters

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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

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Murine adenoviruses: tools for studying adenovirus pathogenesis in a natural host

Cited by 14 publications

References 115 publications

The RGD-binding integrins αvβ6 and αvβ8 are receptors for mouse adenovirus-1 and -3 infection

The RGD-binding integrins αvβ6 and αvβ8 are receptors for mouse adenovirus-1 and -3 infection

A single oral immunization with a replication-competent adenovirus-vectored vaccine protects mice from influenza respiratory infection

Adenoviruses – Infection, pathogenesis and therapy

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