Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of H...Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.展开更多
Introduction: Adenovirus infections are associated with significant morbidity and mortality among immunocompromised hosts. Adenovirus pneumonia is a rare and often fatal disease in patients with AIDS. Case Report: We ...Introduction: Adenovirus infections are associated with significant morbidity and mortality among immunocompromised hosts. Adenovirus pneumonia is a rare and often fatal disease in patients with AIDS. Case Report: We report a case of a 28-year-old woman with advanced HIV/AIDS, who developed pneumonia four weeks after initiation of highly active antiretroviral therapy (HAART). Despite empiric antibiotics, the patient developed worsening hypoxemia and progressive pneumonia on chest x-ray. Culture data from a bronchoalveolar lavage (BAL) was negative for bacteria, fungi, pneumocystis jirovecii, but was positive for adenovirus detected by PCR. After transfer to a tertiary care hospital intensive care unit, a repeat BAL confirmed the presence of adenovirus by immunohistochemical staining. Tissue samples sent for histopathology revealed 'smudge cells'. Serum adenovirus viral load was 1.6 × 105 copies/mL. Intravenous cidofovir, 1 mg/kg/day, was initiated and scheduled three times a week. The patient exhibited remarkable improvement and was discharged to home in stable condition after four doses of cidofovir treatment. Discussion: Prior to our case, the few published accounts of HIV patients with adenovirus pneumonia treated with cidofovir have all resulted in death. Our case is distinct from these cases by the lack of concomitant pulmonary infection and the initiation of HAART prior to presentation. Conclusion: To our knowledge, we present the first case of adenovirus pneumonia in a patient with AIDS successfully treated with cidofovir. Our case suggests that limited and low dose cidofovir may be an efficacious approach to treat adenovirus pneumonia among HIV patients, especially those established on HAART.展开更多
Background: Lower respiratory tract infection (LRTI) is a main cause of hospitalization in infants and children. These patients’ nasopharyngeal swabs more frequently contain respiratory syncytial virus (RSV) than hum...Background: Lower respiratory tract infection (LRTI) is a main cause of hospitalization in infants and children. These patients’ nasopharyngeal swabs more frequently contain respiratory syncytial virus (RSV) than human adenovirus (HAdV) in cold seasons;recent data suggest that oropharyngeal swabs more frequently contain HAdV than RSV. Knowing more about virus detection with oropharyngeal swabs, seasonal fluctuations and age-related distribution of RSV and HAdV would help treat children hospitalized for LRTI more effectively. We investigated the seasonal virus-related frequency (as assessed by oropharyngeal swabs) and environmental and clinical features in infants and children hospitalized for LRTI from autumn to spring. Methods: We studied 98 subjects hospitalized for LRTI in our Pediatric Unit, from November 2006 to May 2007. RSV and HAdV in oropharyngeal swabs were assessed by real-time polymerase chain reaction (PCR) assay. Results: PCR assays more frequently detected HAdV (29.6% of patients) than RSV (25.5%). The seasonal incidence also differed (RSV, narrow peak in December and HAdV, wide peak from April to May). Most patients infected with RSV were aged 2 yrs or younger (23/25: 88%);no difference was found in age between subjects who tested HAdV-positive (13/29: 45%) or undetectable-virus (23/44: 52%). Bronchiolitis was more frequently associated with RSV than HAdV or undetectable-virus oropharyngeal swabs. No difference was found in risk factors (school attendance, atopic parents, exposure to cigarette smoking, home dampness or exposure to animals) or clinical features (vital parameters or duration of hospital stay) among the three viral groups. Conclusions: Our findings show a high frequency of HAdV-positive oropharyngeal swabs during acute LRTIs in infants and children and differences in the seasonal distribution of RSV and HAdV in Rome.展开更多
Human adenovirus type 55(HAdV-B55) is a re-emergent acute respiratory disease pathogen that causes adult communityacquired pneumonia(CAP). Previous studies have shown that the receptor of HAdV-B14, which genome is hig...Human adenovirus type 55(HAdV-B55) is a re-emergent acute respiratory disease pathogen that causes adult communityacquired pneumonia(CAP). Previous studies have shown that the receptor of HAdV-B14, which genome is highly similar with HAdV-B55, is human Desmoglein 2(DSG2). However, whether the receptor of HAdV-B55 is DSG2 is undetermined because there are three amino acid mutations in the fiber gene between HAdV-B14 and HAdV-B55. Here, firstly we found the 3T3 cells, a mouse embryo fibroblast rodent cell line which does not express human DSG2, were able to be infected by HAdV-B55 after transfected with pcDNA3.1-DSG2, while normal 3T3 cells were still unsusceptible to HAdV-B55 infection. Next, A549 cells with h DSG2 knock-down by siRNA were hard to be infected by HAdV-B3/-B14/-B55, while the control siRNA group was still able to be infected by all these types of HAdVs. Finally, immunofluorescence confocal microscopy indicated visually that Cy3-conjugated HAdV-B55 viruses entered A549 cells by binding to DSG2 protein.Therefore, DSG2 is a major receptor of HAdV-B55 causing adult CAP. Our finding is important for better understanding of interactions between adenoviruses and host cells and may shed light on the development of new drugs that can interfere with these processes as well as for the development of potent prophylactic vaccines.展开更多
Objective To better understand the clinical featuresof human adenovirus type 7 (hAdV7) pneumonia and toidentify whether there is a variation in the genome of thestrain ( CHN/BeiJing /2018 ) isolated during the smallsc...Objective To better understand the clinical featuresof human adenovirus type 7 (hAdV7) pneumonia and toidentify whether there is a variation in the genome of thestrain ( CHN/BeiJing /2018 ) isolated during the smallscaleepidemic. Methods Forty-two patients were diagnosedwith hAdV7 pneumonia between October 27th,2017 and February 28th,2018. They were all males withan average age of (21 ± 2) years. Demographic and clinicaldata were reviewed and analyzed in detail. The nucleicacid of the epidemic strain was extracted from abronchoalveolar lavage fluid sample. Whole genome sequencing(WGS ) was then performed and sequenceswere compared with other hAdV7 strains distributed globally.Phylogenetic tree analysis was conducted based onwhole genome sequences of the epidemic strain.展开更多
基金supported by the National Natural Science Foundation of China(No.82073617)Joint Research Fund for Beijing Natural Science Foundation and Haidian Original Innovation(No.L202007)+1 种基金Fundamental Research Funds for the Central Universities and Peking University Health Science Center(No.BMU2021YJ041)Peking University Medicine Fund of Fostering Young Scholars'Scientific&Technological Innovation(No.BMU2021PY005).
文摘Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.
文摘Introduction: Adenovirus infections are associated with significant morbidity and mortality among immunocompromised hosts. Adenovirus pneumonia is a rare and often fatal disease in patients with AIDS. Case Report: We report a case of a 28-year-old woman with advanced HIV/AIDS, who developed pneumonia four weeks after initiation of highly active antiretroviral therapy (HAART). Despite empiric antibiotics, the patient developed worsening hypoxemia and progressive pneumonia on chest x-ray. Culture data from a bronchoalveolar lavage (BAL) was negative for bacteria, fungi, pneumocystis jirovecii, but was positive for adenovirus detected by PCR. After transfer to a tertiary care hospital intensive care unit, a repeat BAL confirmed the presence of adenovirus by immunohistochemical staining. Tissue samples sent for histopathology revealed 'smudge cells'. Serum adenovirus viral load was 1.6 × 105 copies/mL. Intravenous cidofovir, 1 mg/kg/day, was initiated and scheduled three times a week. The patient exhibited remarkable improvement and was discharged to home in stable condition after four doses of cidofovir treatment. Discussion: Prior to our case, the few published accounts of HIV patients with adenovirus pneumonia treated with cidofovir have all resulted in death. Our case is distinct from these cases by the lack of concomitant pulmonary infection and the initiation of HAART prior to presentation. Conclusion: To our knowledge, we present the first case of adenovirus pneumonia in a patient with AIDS successfully treated with cidofovir. Our case suggests that limited and low dose cidofovir may be an efficacious approach to treat adenovirus pneumonia among HIV patients, especially those established on HAART.
文摘Background: Lower respiratory tract infection (LRTI) is a main cause of hospitalization in infants and children. These patients’ nasopharyngeal swabs more frequently contain respiratory syncytial virus (RSV) than human adenovirus (HAdV) in cold seasons;recent data suggest that oropharyngeal swabs more frequently contain HAdV than RSV. Knowing more about virus detection with oropharyngeal swabs, seasonal fluctuations and age-related distribution of RSV and HAdV would help treat children hospitalized for LRTI more effectively. We investigated the seasonal virus-related frequency (as assessed by oropharyngeal swabs) and environmental and clinical features in infants and children hospitalized for LRTI from autumn to spring. Methods: We studied 98 subjects hospitalized for LRTI in our Pediatric Unit, from November 2006 to May 2007. RSV and HAdV in oropharyngeal swabs were assessed by real-time polymerase chain reaction (PCR) assay. Results: PCR assays more frequently detected HAdV (29.6% of patients) than RSV (25.5%). The seasonal incidence also differed (RSV, narrow peak in December and HAdV, wide peak from April to May). Most patients infected with RSV were aged 2 yrs or younger (23/25: 88%);no difference was found in age between subjects who tested HAdV-positive (13/29: 45%) or undetectable-virus (23/44: 52%). Bronchiolitis was more frequently associated with RSV than HAdV or undetectable-virus oropharyngeal swabs. No difference was found in risk factors (school attendance, atopic parents, exposure to cigarette smoking, home dampness or exposure to animals) or clinical features (vital parameters or duration of hospital stay) among the three viral groups. Conclusions: Our findings show a high frequency of HAdV-positive oropharyngeal swabs during acute LRTIs in infants and children and differences in the seasonal distribution of RSV and HAdV in Rome.
基金This work was supported by grants from the National Key Research and Development Program of China(2018YFE0204503)Natural Science Foundation of Guangdong Province(2021A1515010788 and 2018B030312010)the Guangzhou Healthcare Collaborative Innovation Major Project(201803040004 and 201803040007)。
文摘Human adenovirus type 55(HAdV-B55) is a re-emergent acute respiratory disease pathogen that causes adult communityacquired pneumonia(CAP). Previous studies have shown that the receptor of HAdV-B14, which genome is highly similar with HAdV-B55, is human Desmoglein 2(DSG2). However, whether the receptor of HAdV-B55 is DSG2 is undetermined because there are three amino acid mutations in the fiber gene between HAdV-B14 and HAdV-B55. Here, firstly we found the 3T3 cells, a mouse embryo fibroblast rodent cell line which does not express human DSG2, were able to be infected by HAdV-B55 after transfected with pcDNA3.1-DSG2, while normal 3T3 cells were still unsusceptible to HAdV-B55 infection. Next, A549 cells with h DSG2 knock-down by siRNA were hard to be infected by HAdV-B3/-B14/-B55, while the control siRNA group was still able to be infected by all these types of HAdVs. Finally, immunofluorescence confocal microscopy indicated visually that Cy3-conjugated HAdV-B55 viruses entered A549 cells by binding to DSG2 protein.Therefore, DSG2 is a major receptor of HAdV-B55 causing adult CAP. Our finding is important for better understanding of interactions between adenoviruses and host cells and may shed light on the development of new drugs that can interfere with these processes as well as for the development of potent prophylactic vaccines.
文摘Objective To better understand the clinical featuresof human adenovirus type 7 (hAdV7) pneumonia and toidentify whether there is a variation in the genome of thestrain ( CHN/BeiJing /2018 ) isolated during the smallscaleepidemic. Methods Forty-two patients were diagnosedwith hAdV7 pneumonia between October 27th,2017 and February 28th,2018. They were all males withan average age of (21 ± 2) years. Demographic and clinicaldata were reviewed and analyzed in detail. The nucleicacid of the epidemic strain was extracted from abronchoalveolar lavage fluid sample. Whole genome sequencing(WGS ) was then performed and sequenceswere compared with other hAdV7 strains distributed globally.Phylogenetic tree analysis was conducted based onwhole genome sequences of the epidemic strain.
