Clinical Features, Replication Competence, and Innate Immune Responses of Human Adenovirus Type 7 Infection

Chen, Qigao; Liu, Jun; Liang, Weiwen; Chen, Yi; Dou, Min; Liu, Zhongmin; Chen, Yuan; Zheng, Zhongli; Zhu, Bing; Lin, Yongping

doi:10.1093/infdis/jiaa524

Cited by 23 publications

(18 citation statements)

References 28 publications

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“…HAdVs are considered the common viral agent of pediatric severe pneumonia, with HAdV-7 in particular causing more severe clinical consequences [38], which is often associated with the high replication competence of HAdV-7 in human lung [39], and prolonged virus shedding and persistence of HAdV-7 in targeting cell [40]. Some of which possible mechanisms have been previously reported.…”

Section: Discussionmentioning

confidence: 99%

Identifying the functional pathways and potential genes associated with interferon signaling during human adenovirus type 7 (HAdV-7) by weighted gene co-expression network analysis

Yang

Wei

et al. 2022

Preprint

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Background Human adenovirus type 7 (HAdV-7) can cause severe pneumonia in children and severe complications. At present, however, the pathogenesis and genes involved remain largely unknown. Methods We collected HAdV-7 infected and mock-infected A549 cells at 24, 48, and 72 hours post-infection (hpi) for RNA sequencing (RNA-seq). And, we identified potential genes and functional pathways associated with HAdV-7 infection using weighted gene co-expression network analysis (WGCNA). Results Based on bioinformatics analysis, 12 co-expression modules were constructed by WGCNA, with the blue, tan, and brown modules significantly positively correlated with Ad-24 hpi, Ad-48 hpi, and Ad-72 hpi, respectively. Functional enrichment analysis indicated that the blue module was mainly enriched in DNA replication, cell cycle, and viral process; the tan module was largely enriched in metabolic pathways and regulation of superoxide radical removal; and the brown module was predominantly enriched in mitochondrial respiratory chains and regulation of cell death. Quantitative polymerase chain reaction (qPCR) was used to determine transcript abundance of some identified hub genes, and results were consistent with those from RNA-seq. Based on comprehensive analysis of hub genes and differentially expressed genes (DEGs) in the GSE68004 dataset, we identified SOCS3, OASL, ISG15, and IFIT1 as potential candidate genes for biomarkers or drug targeting in HAdV-7 infection. Further, we propose a multi-target inhibition of interferon signaling mechanism to explain the HAdV-7 associated with higher severity of clinical consequences. Conclusions We constructed a framework of co-expression gene modules from A549 cells infected with HAdV-7, thus providing a basis for identifying potential genes and pathways involved in adenovirus infection and for studying the pathogenesis of adenoviruses.

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Section: Discussionmentioning

confidence: 99%

Identifying the functional pathways and potential genes associated with interferon signaling during human adenovirus type 7 (HAdV-7) by weighted gene co-expression network analysis

Yang

Wei

et al. 2022

Preprint

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“…HAdVs, a common cause of acute respiratory diseases, is a double-stranded linear DNA virus with a diameter of 70–90 nm. Life-threatening HAdV pneumonia has been recorded in military employees, AIDS patients, and transplant recipients ( Chen et al., 2020 ). Due to the innate characteristics of DNA, HAdVs are strongly resistant to general environmental changes and are difficult to inactivate.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Immunological Characteristics of Patients With Adenovirus Infection at Different Altitude Areas in Tibet, China

Wang

Peng

et al. 2021

Front. Cell. Infect. Microbiol.

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BackgroundThe severities of human adenovirus (HAdV) infection are diverse in different areas of Tibet, China, where a large altitude span emerges. Serious consequences may be caused by medical staff if the clinical stages and immunological conditions of patients in high-altitude areas are misjudged. However, the clinical symptoms, immunological characteristics, and environmental factors of HAdV infection patients at different altitude areas have not been well described.MethodsIn this retrospective, multicenter cohort study, we analyzed the data of patients who were confirmed HAdV infection by PCR tests in the General Hospital of Tibet Military Command or CDC (the Center for Disease Control and Prevention) of Tibet Military Command from January 1, 2019, to December 31, 2020. Demographic, clinical, laboratory, radiological, and epidemiological data were collected from medical records system and compared among different altitude areas. The inflammatory cytokines as well as the subsets of monocytes and regulatory T cells of patients were also obtained and analyzed in this study.ResultsSix hundred eighty-six patients had been identified by laboratory-confirmed HAdV infection, including the low-altitude group (n = 62), medium-altitude group (n = 206), high-altitude group (n = 230), and ultra-high-altitude group (n = 188). Referring to the environmental factors regression analysis, altitude and relative humidity were tightly associated with the number of infected patients (P < 0.01). A higher incidence rate of general pneumonia (45.7%) or severe pneumonia (8.0%) occurred in the ultra-high-altitude group (P < 0.05). The incubation period, serial interval, course of the disease, and PCR-positive duration were prolonged to various extents compared with the low-altitude group (P < 0.05). Different from those in low-altitude areas, the levels of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, TNF-α, TNF-β, and VEGF in the plasma of the ultra-high-altitude group were increased (P < 0.05), while the proportion of non-classical monocytes and regulatory T cells was decreased (P < 0.05).ConclusionsThe findings of this research indicated that patients with HAdV infection in high-altitude areas had severe clinical symptoms and a prolonged course of disease. During clinical works, much more attention should be paid to observe the changes in their immunological conditions. Quarantine of patients in high-altitude areas should be appropriately extended to block virus shedding.

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“…However, infections with some human species B adenoviruses (e.g., HAdV-B3 and HAdV-B7) can lead to severe respiratory illness and manifest as pneumonia and acute respiratory distress syndrome (ARDS) [ 14 ]. Recently, the levels of cytokines and chemokines in plasma and bronchoalveolar lavage fluid (BALF) in immunocompetent adult and pediatric patient cohorts with pneumonia and ARDS caused by HAdV-B3 and HAdV-B7 infections were reported [ 15 , 16 , 17 , 18 ]. The amounts and the profiles of cyto-kines were determined in these patient cohorts were cytokines with potent pro-inflammatory properties, including IL-1α, IL-1β, IL-6, IL-8, IL-12, IFN-γ, IFN-α2, TNF-α, and chemokines CCL2, CCL3, and CXCL10.…”

Section: Cytokine Responses To Adenovirus In Different Biological Con...mentioning

confidence: 99%

“…Moreover, the cytokine profiles produced in response to adenovirus in the in vitro infection models of human or monkey PBMC, lung cultures, or blood-derived dendritic cells are also similar to those detected after vaccination, natural infection, or i.v. administration of adenovirus vector ( Figure 1 , In vitro models) [ 17 , 53 , 54 , 55 ]. The stereotypic nature of the innate immune response to adenovirus in diverse biological contexts strongly suggest that the activation of pro-inflammatory cytokines and chemokines in response to adenovirus is driven in different systems by the same molecular mechanisms.…”

Section: Cytokine Responses To Adenovirus In Different Biological Con...mentioning

confidence: 99%

“…dLN—draining lymph node; BAL—bronchoalveolar lavage; n/a—data are not available; n/d—non detected; #—in this study, the virus was delivered intratracheally. The data for individual cytokines and chemokines, reported in references from [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ...…”

Section: Figurementioning

confidence: 99%

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Cytokine Responses to Adenovirus and Adenovirus Vectors

Atasheva

Shayakhmetov

2022

Viruses

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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.

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Clinical Features, Replication Competence, and Innate Immune Responses of Human Adenovirus Type 7 Infection

Cited by 23 publications

References 28 publications

Identifying the functional pathways and potential genes associated with interferon signaling during human adenovirus type 7 (HAdV-7) by weighted gene co-expression network analysis

Identifying the functional pathways and potential genes associated with interferon signaling during human adenovirus type 7 (HAdV-7) by weighted gene co-expression network analysis

Clinical and Immunological Characteristics of Patients With Adenovirus Infection at Different Altitude Areas in Tibet, China

Cytokine Responses to Adenovirus and Adenovirus Vectors

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