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FEBS Letters Jun 2020Both well-known and emerging viruses increasingly affect humans and cause disease, sometimes with devastating impact on society. The viruses present in the biosphere are...
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-the-art 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.
Topics: Adenoviridae; Adenoviridae Infections; Animals; Host-Pathogen Interactions; Humans; Virus Internalization
PubMed: 32538496
DOI: 10.1002/1873-3468.13849 -
Seminars in Respiratory and Critical... Dec 2021Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare...
Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The vast majority of cases are self-limited. However, the clinical spectrum is broad and fatalities may occur. Dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 100 genotypes and 52 serotypes of AdV have been identified and classified into seven species designated HAdV-A through -G. Different types display different tissue tropisms that correlate with clinical manifestations of infection. The predominant types circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been done. Cidofovir has been the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States but currently are not available to civilians.
Topics: Adenoviridae; Adenoviridae Infections; Adult; Child; Child, Preschool; Cidofovir; Humans; Prospective Studies; Respiratory Tract Infections; United States
PubMed: 34918322
DOI: 10.1055/s-0041-1733802 -
Clinical Transplantation Sep 2019These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management...
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of adenovirus infections after solid organ transplantation. Adenovirus is an important cause of infectious complications in both stem cell transplant and SOT patients, causing a range of clinical syndromes including pneumonitis, colitis, and disseminated disease. The current update of the guidelines highlights that adenovirus surveillance testing should not be performed in asymptomatic recipients. Serial quantitative PCR might play a role in the decision to initiate or assess response to therapy in a symptomatic patient. The initial and most important components of therapy remain supportive care and decrease in immunosuppression. The use of antiviral therapy is not supported by prospective randomized clinical trials. However, intravenous cidofovir is considered the standard practice for treatment of severe, progressive, or disseminated adenovirus disease in most transplant centers. Intravenous immunoglobulin may be beneficial, primarily in a select group of patients with hypogammaglobulinemia. Future approaches to treatment of adenovirus disease may include administration of adenovirus-specific T-cell therapy.
Topics: Adenoviridae; Adenoviridae Infections; Antiviral Agents; Humans; Organ Transplantation; Practice Guidelines as Topic; Societies, Medical; Transplant Recipients
PubMed: 30859626
DOI: 10.1111/ctr.13527 -
PLoS Pathogens Nov 2020Enteric alpha-defensins are potent effectors of innate immunity that are abundantly expressed in the small intestine. Certain enteric bacteria and viruses are resistant...
Enteric alpha-defensins are potent effectors of innate immunity that are abundantly expressed in the small intestine. Certain enteric bacteria and viruses are resistant to defensins and even appropriate them to enhance infection despite neutralization of closely related microbes. We therefore hypothesized that defensins impose selective pressure during fecal-oral transmission. Upon passaging a defensin-sensitive serotype of adenovirus in the presence of a human defensin, mutations in the major capsid protein hexon accumulated. In contrast, prior studies identified the vertex proteins as important determinants of defensin antiviral activity. Infection and biochemical assays suggest that a balance between increased cell binding and a downstream block in intracellular trafficking mediated by defensin interactions with all of the major capsid proteins dictates the outcome of infection. These results extensively revise our understanding of the interplay between defensins and non-enveloped viruses. Furthermore, they provide a feasible rationale for defensins shaping viral evolution, resulting in differences in infection phenotypes of closely related viruses.
Topics: A549 Cells; Adenoviridae; Adenoviridae Infections; Antiviral Agents; Capsid Proteins; Evolution, Molecular; Humans; Immunity, Innate; Intestine, Small; Models, Molecular; Mutation; Serogroup; alpha-Defensins
PubMed: 33232373
DOI: 10.1371/journal.ppat.1009018 -
Viruses Apr 2022The expression of cytokines and chemokines in response to adenovirus infection is tightly regulated by the innate immune system. Cytokine-mediated toxicity and cytokine... (Review)
Review
The expression of cytokines and chemokines in response to adenovirus infection is tightly regulated by the innate immune system. Cytokine-mediated toxicity and cytokine storm are known clinical phenomena observed following naturally disseminated adenovirus infection in immunocompromised hosts as well as when extremely high doses of adenovirus vectors are injected intravenously. This dose-dependent, cytokine-mediated toxicity compromises the safety of adenovirus-based vectors and represents a critical problem, limiting their utility for gene therapy applications and the therapy of disseminated cancer, where intravenous injection of adenovirus vectors may provide therapeutic benefits. The mechanisms triggering severe cytokine response are not sufficiently understood, prompting efforts to further investigate this phenomenon, especially in clinically relevant settings. In this review, we summarize the current knowledge on cytokine and chemokine activation in response to adenovirus- and adenovirus-based vectors and discuss the underlying mechanisms that may trigger acute cytokine storm syndrome. First, we review profiles of cytokines and chemokines that are activated in response to adenovirus infection initiated via different routes. Second, we discuss the molecular mechanisms that lead to cytokine and chemokine transcriptional activation. We further highlight how immune cell types in different organs contribute to synthesis and systemic release of cytokines and chemokines in response to adenovirus sensing. Finally, we review host factors that can limit cytokine and chemokine expression and discuss currently available and potential future interventional approaches that allow for the mitigation of the severity of the cytokine storm syndrome. Effective cytokine-targeted interventional approaches may improve the safety of systemic adenovirus delivery and thus broaden the potential clinical utility of adenovirus-based therapeutic vectors.
Topics: Adenoviridae; Adenoviridae Infections; Chemokines; Cytokine Release Syndrome; Cytokines; Humans; Immunity, Innate
PubMed: 35632630
DOI: 10.3390/v14050888 -
American Journal of Transplantation :... Jul 2022
Topics: Acute Disease; Adenoviridae Infections; Alabama; Child; Hepatitis; Humans
PubMed: 35789534
DOI: 10.1111/ajt.16665 -
Viruses Feb 2021Human adenoviruses cause disease at multiple mucosal sites, including the respiratory, gastrointestinal, and genitourinary tracts, and are common agents of... (Review)
Review
Human adenoviruses cause disease at multiple mucosal sites, including the respiratory, gastrointestinal, and genitourinary tracts, and are common agents of conjunctivitis. One site of infection that has received sparse attention is the cornea, a transparent tissue and the window of the eye. While most adenovirus infections are self-limited, corneal inflammation (keratitis) due to adenovirus can persist or recur for months to years after infection, leading to reduced vision, discomfort, and light sensitivity. Topical corticosteroids effectively suppress late adenovirus keratitis but are associated with vision-threatening side effects. In this short review, we summarize current knowledge on infection of the cornea by adenoviruses, including corneal epithelial cell receptors and determinants of corneal tropism. We briefly discuss mechanisms of stromal keratitis due to adenovirus infection, and review an emerging therapy to mitigate adenovirus corneal infections based on evolving knowledge of corneal epithelial receptor usage.
Topics: Adenoviridae Infections; Adenoviruses, Human; Animals; Cornea; Corneal Diseases; Humans
PubMed: 33668417
DOI: 10.3390/v13020293 -
Transplant Infectious Disease : An... Nov 2023Adenovirus (AdV) infection occurs in 0-20% of patients in the first 3-4 months after allogeneic hematopoietic cell transplantation (HCT), being higher in pediatric than... (Review)
Review
Adenovirus (AdV) infection occurs in 0-20% of patients in the first 3-4 months after allogeneic hematopoietic cell transplantation (HCT), being higher in pediatric than in adult patients. About 50% of AdV infections involve the blood, which in turn, correlates with an increased risk developing AdV diseases, end-organ damage, and 6-month overall mortality. The main risk factors for AdV infection are T-cell depletion of the graft by ex vivo selection procedures or in vivo use of alemtuzumab or antithymocyte serum, development of graft versus host disease (GVHD) grade III-IV, donor type (haploidentical or human leucocyte antigen mismatched related donor > cord blood> unrelated matched donor) and severe lymphopenia (<0.2 × 10 /L). The prevention of AdV disease relies on early diagnosis of increasing viral replication in blood or stool and the pre-emptive start of cidofovir as viral load exceeds the threshold of ≥10 copies/mL in blood and/or 10 copies/g stool in the stool. Cidofovir (CDV), a cytosine monophosphate nucleotide analog, is currently the only antiviral recommended for AdV infection despite limited efficacy and moderate risk of nephrotoxicity. Brincidofovir, a lipid derivative of CDV with more favorable pharmacokinetics properties and superior efficacy, is not available and currently is being investigated for other viral infections. The enhancement of virus-specific T-cell immunity in the first few months post-HCT by the administration of donor-derived or third-party-donor-derived virus-specific T-cells represents an innovative and promising modality of intervention and data of efficacy and safety of the ongoing prospective randomized studies are eagerly awaited.
Topics: Adult; Humans; Child; Cidofovir; Prospective Studies; Adenoviridae Infections; Risk Factors; Immunologic Factors; Hematopoietic Stem Cell Transplantation
PubMed: 37846850
DOI: 10.1111/tid.14173 -
Viruses Jun 2021Adenovirus is a common cause of disease in humans and in animals [...].
Adenovirus is a common cause of disease in humans and in animals [...].
Topics: Adenoviridae; Adenoviridae Infections; Adenoviruses, Human; Animals; Disease Models, Animal; Humans
PubMed: 34200540
DOI: 10.3390/v13061112 -
The New England Journal of Medicine Aug 2023
Topics: Humans; Adenoviridae; Adenoviridae Infections; Antibodies; Thrombocytopenia; Thrombosis; Purpura, Thrombocytopenic, Idiopathic; Adenovirus Vaccines
PubMed: 37590457
DOI: 10.1056/NEJMc2307721