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Transplantation May 2022Adenoviruses result in a wide array of clinical presentations, including primarily respiratory, gastrointestinal, genitourinary, or systemic infections. Although...
Adenoviruses result in a wide array of clinical presentations, including primarily respiratory, gastrointestinal, genitourinary, or systemic infections. Although adenovirus causes mild disease limited to a single organ system in immunocompetent individuals, severe and life-threatening infections do rarely occur. Disseminated disease and severe localized disease resulting in significant morbidity and mortality have been well described in the immunocompromised populations. Although asymptomatic viremia, respiratory tract, and gastrointestinal infections are the most common disease in most transplant patients, renal transplant patients more commonly experience urinary tract infections, including hemorrhagic cystitis or nephritis. Diagnosis requires astute clinical awareness of the patient's clinical presentation that would be compatible with adenovirus combined with cultures, molecular testing, polymerase chain reaction, and tissue sampling. There is no Food and Drug Administration-approved treatment for adenovirus; however, several studies have evaluated therapeutic options including cidofovir, brincidofovir, and immunotherapy. This article will summarize our current understanding of adenovirus in the transplant population.
Topics: Adenoviridae; Adenoviridae Infections; Antiviral Agents; Humans; Immunocompromised Host; Kidney Transplantation; Viremia
PubMed: 34856601
DOI: 10.1097/TP.0000000000003988 -
FEBS Letters Dec 2019Incoming adenoviruses seize control of cytosolic transport mechanisms to relocate their genome from the cell periphery to specialized sites in the nucleoplasm. The... (Review)
Review
Incoming adenoviruses seize control of cytosolic transport mechanisms to relocate their genome from the cell periphery to specialized sites in the nucleoplasm. The nucleus is the site for viral gene expression, genome replication, and the production of progeny for the next round of infection. By taking control of the cell, adenoviruses also suppress cell-autonomous immunity responses. To succeed in their production cycle, adenoviruses rely on well-coordinated steps, facilitated by interactions between viral proteins and cellular factors. Interactions between virus and host can impose remarkable morphological changes in the infected cell. Imaging adenoviruses has tremendously influenced how we delineate individual steps in the viral life cycle, because it allowed the development of specific optical markers to label these morphological changes in space and time. As technology advances, innovative imaging techniques and novel tools for specimen labeling keep uncovering previously unseen facets of adenovirus biology emphasizing why imaging adenoviruses is as attractive today as it was in the past. This review will summarize past achievements and present developments in adenovirus imaging centered on fluorescence microscopy approaches.
Topics: Adenoviridae; Adenoviridae Infections; Cell Nucleus; Cryoelectron Microscopy; Host-Pathogen Interactions; Humans; Microscopy, Atomic Force; Viral Proteins; Virus Replication
PubMed: 31758703
DOI: 10.1002/1873-3468.13690 -
Microbiology Spectrum Aug 2016Adenoviruses are a highly prevalent infection that can cause a range of clinical syndromes in immunocompromised patients, ranging from localized disease of the... (Review)
Review
Adenoviruses are a highly prevalent infection that can cause a range of clinical syndromes in immunocompromised patients, ranging from localized disease of the respiratory tract, gastrointestinal tract, or urinary tract to disseminated disease. Adenovirus infections may develop in this unique population as the result of primary infection or reactivation of latent virus. Disease can be potentially progressive with high rates of mortality in patients with pneumonia and disseminated disease. Fortunately, cidofovir and its lipid ester, brincidofovir, appear to be effective for the treatment of adenovirus, although neither is specifically approved for this indication. Adenovirus should always be considered when immunocompromised patients present with any clinical syndrome that could be compatible with adenoviral infection. Once disease is suspected, cultures or molecular testing of appropriate specimens should be obtained and blood should be sent for adenovirus polymerase chain reaction (PCR) whenever adenovirus is suspected. Monitoring of quantitative viral loads in blood is helpful in predicting response to therapy with a significant drop (>1 log) associated with a higher probability of clinical response.
Topics: Adenoviridae Infections; Antiviral Agents; Cidofovir; Cytosine; Diagnostic Tests, Routine; Disease Susceptibility; Drug Monitoring; Humans; Immunocompromised Host; Organophosphonates
PubMed: 27726766
DOI: 10.1128/microbiolspec.DMIH2-0020-2015 -
Seminars in Respiratory and Critical... Aug 2016Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare... (Review)
Review
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 disease is more severe and 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 50 serotypes of AdV have been identified. Different serotypes display different tissue tropisms that correlate with clinical manifestations of infection. The predominant serotypes 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 conducted. Cidofovir is 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; Adenovirus Infections, Human; Adult; Antiviral Agents; Child; Cidofovir; Cytosine; Humans; Military Personnel; Organophosphonates; Prospective Studies; Respiratory Tract Infections; Serogroup; Viral Vaccines
PubMed: 27486739
DOI: 10.1055/s-0036-1584923 -
World Journal of Pediatrics : WJP Aug 2022Outbreaks of severe, acute hepatitis among children have recently attracted global attention. The pathogen causing the outbreak remains unknown, but there is growing... (Review)
Review
BACKGROUND
Outbreaks of severe, acute hepatitis among children have recently attracted global attention. The pathogen causing the outbreak remains unknown, but there is growing evidence that it may be associated with human adenovirus (HAdV).
DATA SOURCES
A review of adenovirus-related clinical studies, epidemiological studies, etiological studies, and case reports was conducted by reviewers independently.
RESULTS
HAdV can cause a wide variety of clinical symptoms. In the Mainland of China, HAdV infection accounts for 5.8%-13% of patients with acute respiratory infections, and these infections are mainly caused by species B, C, and E of HAdV. For acute conjunctivitis, 39.8%-74.9% of sporadic cases were infected by B and D species of HAdV. Outbreaks of keratoconjunctivitis and pharyngoconjunctival fever related to HAdV infection could be found throughout the country. In pediatric patients with acute gastroenteritis, HAdV-41 was the predominant HAdV type, followed by HAdV species B and C. Several types of HAdV, including HAdV-5, HAdV-7, HAdV-1, and HAdV-2, have previously been reported as potential pathogens associated with HAdV hepatitis in immunocompromised patients. However, few HAdV-related hepatitis cases have been reported in China to date.
CONCLUSIONS
There are no systematic surveillance and clinical studies on HAdV hepatitis in China. Therefore, it is imperative to establish a nationwide HAdV virological surveillance system to collect relevant clinical, epidemiological and virological surveillance data and risk factor information as soon as possible to assess the potential risk of HAdV hepatitis among children.
Topics: Acute Disease; Adenoviridae Infections; Adenovirus Infections, Human; Child; China; Humans; Phylogeny; Respiratory Tract Infections
PubMed: 35716276
DOI: 10.1007/s12519-022-00568-8 -
Clinical Microbiology Reviews Jul 2014Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical... (Review)
Review
Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical challenges pertaining to diagnostics and treatment. The growing number of HAdV types identified by genomic analysis, as well as the improved understanding of the sites of viral persistence and reactivation, requires continuous adaptions of diagnostic approaches to facilitate timely detection and monitoring of HAdV infections. In view of the clinical relevance of life-threatening HAdV diseases in the immunocompromised setting, there is an urgent need for highly effective treatment modalities lacking major side effects. The present review summarizes the recent progress in the understanding and management of HAdV infections.
Topics: Adenoviridae Infections; Adenoviruses, Human; Animals; Host-Pathogen Interactions; Humans; Immunocompromised Host; Incidence; Risk Factors
PubMed: 24982316
DOI: 10.1128/CMR.00116-13 -
Infection Feb 2021The clinical characteristics of various adenovirus (ADV) infection are underexplored up till now. To investigate the risk factors, manifestation, current status of ADV... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The clinical characteristics of various adenovirus (ADV) infection are underexplored up till now. To investigate the risk factors, manifestation, current status of ADV species, treatment and prognosis of this disease.
METHODS
We performed a Pubmed and Embase systematic review for case report reporting the ADV infection to analyze the clinical characteristics of disease.
RESULTS
Initial database searched identified articles of which 168 (228 cases) were included in the final analysis. Previous solid organ transplantation [odds ratio (OR) = 3.45, 95% CI 1.31-9.08, P = 0.01], hematopoietic stem cell transplant (OR = 4.24, 95% CI 1.33-13.51, P = 0.01) and hematological malignancy (OR = 4.78, 95% CI 1.70-13.46, P = 0.01) were associated with increased risk of disseminated ADV infection. Use of corticosteroids (OR = 3.86, 95% CI 1.21-12.24, P = 0.02) was a significant risk factor for acquiring urinary tract infections. A total of six species (21 types) of ADV infection have been identified in 100/228 (43.9%) cases. ADV B was the most common species. ADV B species (26/60, 52.0% or 5/41, 12.2% P = 0.001) were more isolated in patients with ADV pneumonia. ADV C (13/15, 86.7% versus 35/86, 40.7% P = 0.001) species were more identified in patients with disseminated disease. The species associated with keratoconjunctivitis is only ADV D in our analysis. Urinary tract ADV infections were observed in ADV A/B/D species. Cidofovir (CDV) (82/228, 36.0%) remained the most commonly antiviral therapy in our cases, followed by ribavirin (15/228, 6.6%), ganciclovir (18/228, 7.9%), and brincidofovir (12/228, 5.3%). Brincidofovir was administered as salvage therapy in 10 cases. Death was reported in 81/228 (35.5%) patients. Mortality rate was higher among patients with gastrointestinal (GI) ADV infection (5/10, 50.0%), ADV pneumonia (20/45, 44.4%) and disseminated ADV infection (53/122, 43.4%).
CONCLUSION
Previous solid organ transplantation, hematopoietic stem cell transplant and hematological malignancy were risk factors for disseminated ADV infection. Use of corticosteroids was significant for urinary tract ADV infection. Different species correlated with different clinical manifestations of infection. Mortality rate was higher among patients with GI disease, pneumonia and disseminated disease. Our review clarified the current treatment of ADV infections, and more treatment required further investigation.
Topics: Adenoviridae; Adenoviridae Infections; Adult; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Organ Transplantation; Risk Factors
PubMed: 32720128
DOI: 10.1007/s15010-020-01484-7 -
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 -
American Journal of Transplantation :... Jul 2022
Topics: Acute Disease; Adenoviridae Infections; Alabama; Child; Hepatitis; Humans
PubMed: 35789534
DOI: 10.1111/ajt.16665 -
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