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Adenovirus infections [keywords]
- Etiology of Maculopapular Rash in Measles and Rubella Suspected Patients from Belarus. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e111541.
As a result of successful implementation of the measles/rubella elimination program, the etiology of more and more double negative cases remains elusive. The present study determined the role of different viruses as causative agents in measles or rubella suspected cases in Belarus. A total of 856 sera sent to the WHO National Laboratory between 2009 and 2011 were tested for specific IgM antibodies to measles virus (MV), rubella virus (RV) and human parvovirus B19 (B19V). The negatives were further investigated for antibodies to enterovirus (EV) and adenovirus (AdV). Children of up to 3 years were tested for IgM antibodies to human herpesvirus 6 (HHV6). A viral etiology was identified in 451 (52.7%) cases, with 6.1% of the samples being positive for MV; 2.6% for RV; 26.2% for B19V; 9.7% for EV; 4.6% for AdV; and 3.6% for HHV6. Almost all measles and rubella cases occurred during limited outbreaks in 2011 and nearly all patients were at least 15 years old. B19V, EV and AdV infections were prevalent both in children and adults and were found throughout the 3 years. B19V occurred mainly in 3-10 years old children and 20-29 years old adults. EV infection was most common in children up to 6 years of age and AdV was confirmed mainly in 3-6 years old children. HHV6 infection was mostly detected in 6-11 months old infants. Laboratory investigation of measles/rubella suspected cases also for B19V, EV, AdV and HHV6 allows diagnosing more than half of all cases, thus strengthening rash/fever disease surveillance in Belarus.
- ADV36 adipogenic adenovirus in human liver disease. [REVIEW]
- World J Gastroenterol 2014 Oct 28; 20(40):14706-14716.
Obesity and liver steatosis are usually described as related diseases. Obesity is regarded as exclusive consequence of an imbalance between food intake and physical exercise, modulated by endocrine and genetic factors. Non-alcoholic fatty liver disease (NAFLD), is a condition whose natural history is related to, but not completely explained by over-nutrition, obesity and insulin resistance. There is evidence that environmental infections, and notably adipogenic adenoviruses (ADV) infections in humans, are associated not only with obesity, which is sufficiently established, but also with allied conditions, such as fatty liver. In order to elucidate the role, if any, of previous ADV36 infection in humans, we investigated association of ADV36-ADV37 seropositivity with obesity and fatty liver in humans. Moreover, the possibility that lifestyle-nutritional intervention in patients with NAFLD and different ADV36 seropositive status, achieves different clinical outcomes on ultrasound bright liver imaging, insulin resistance and obesity was challenged. ADV36 seropositive patients have a more consistent decrease in insulin resistance, fatty liver severity and body weight in comparison with ADV36 seronegative patients, indicating a greater responsiveness to nutritional intervention. These effects were not dependent on a greater pre-interventional body weight and older age. These results imply that no obvious disadvantage - and, seemingly, that some benefit - is linked to ADV36 seropositivity, at least in NAFLD. ADV36 previous infection can boost weight loss and recovery of insulin sensitivity under interventional treatment.
- Amplified and Persistent Immune Responses Generated by Single Cycle Replicating Adenovirus Vaccines. [JOURNAL ARTICLE]
- J Virol 2014 Oct 29.
Replication-competent adenoviral vectors (RC-Ad) generate exceptionally strong gene-based vaccine responses by amplifying the antigen transgenes they carry. While they are potent, they also risk causing adenovirus infections. More common E1-deleted replication-defective Ad (RD-Ad) vectors avoid this risk, but do not replicate their transgene and generate markedly weaker vaccine responses. To amplify vaccine transgenes while avoiding production of infectious progeny viruses, we engineered "single cycle" adenovirus (SC-Ad) vectors by deleting the gene for IIIa capsid cement protein of lower seroprevalence adenovirus serotype 6. In mouse, human, hamster, and macaque cells, SC-Ad6 still replicated its genome, but prevented genome packaging and virion maturation. When used for mucosal intranasal immunization of Syrian hamsters, both SC-Ad and RC-Ad expressed transgenes hundreds of times higher than RD-Ad. Surprisingly, SC-Ad, but not RC-Ad generated higher transgene-specific antibody levels than RD-Ad, which notably climbed in serum and vaginal wash samples over 12 weeks after single mucosal immunization. When RD-Ad and SC-Ad were tested by single sublingual immunization in rhesus macaques, SC-Ad generated higher IFN-γ responses and higher transgene-specific serum antibody levels. These data suggest SC-Ad vectors may have utility as mucosal vaccines.This work illustrates the utility of our recently developed single cycle adenovirus (SC-Ad6) vector as a new vaccine platform. Replication defective (RD-Ad6) vectors produce low levels of transgene protein, which leads to minimal antibody responses in vivo. This study shows replicating SC-Ad6 produces higher levels of luciferase and induces higher GFP-specific antibodies than RD in a permissive Syrian hamster model. Surprisingly, although a replication competent (RC-Ad6) vector produces more luciferase than SC-Ad6, it does not elicit comparable anti-GFP antibodies in permissive hamsters. When tested in the larger rhesus macaque model, SC-Ad6 induces higher transgene-specific antibody and T cell responses. Together this data suggests SC-Ad6 could be a more effective platform for developing vaccines against more relevant antigens. This could be especially beneficial for developing vaccines for pathogens where traditional replication defective adenovirus vectors have not been effective.
- DNA microarray for detection of gastrointestinal viruses. [JOURNAL ARTICLE]
- J Clin Microbiol 2014 Oct 29.
Gastroenteritis is a clinical illness of humans and other animals characterized by vomiting and diarrhea, caused by a variety of pathogens including viruses. An increasing number of viral species have been associated with gastroenteritis or have been found in stool samples as new molecular tools are developed. In this work, a DNA microarray capable in theory of parallel detection of more than 100 viral species was developed and tested. Initial validation was done with 10 different virus species and an additional 5 species were validated using clinical samples. Detection limits of 1x10(3) virus particles of human adenovirus C (HAdV), human astrovirus (HAstV) and group A rotavirus (RV-A) were established. Furthermore, when exogenous RNA was added, the limit for RV-A detection decreased in one log. In a small group of clinical samples from children with gastroenteritis (n = 76), the microarray detected at least one viral species in 92% of the samples. Single infection was identified in 63 samples (83%) and more than one virus was identified in 7 samples (9%). The most abundant virus species were RV-A (58%), followed by anellovirus (15.8%), HAstV (6.6%), HAdV (5.3%), Norwalk virus (6.6%), human enterovirus (HEV; 9.2%), human parechovirus (1.3%), Sapporo virus (1.3%) and human bocavirus (1.3%). To further test the specificity and sensitivity of the microarray, the results were verified by RT-PCR detection of 5 gastrointestinal viruses. The RT- PCR assay detected a virus in 59 samples (78%). The microarray showed good performance for detection of RV-A, HAstV and calicivirus, while the sensitivity for HAdV and HEV was low. Furthermore some discrepancies in detection of mixed infections were observed, and were addressed by RT-qPCR of the viruses involved. It was observed that differences in the amount of genetic material favored the detection of the most abundant virus. The microarray described in this work should help to understand the etiology of gastroenteritis in humans and animals.
- [Respiratory virus infections in adult patients hospitalized in an internal medicine unit]. [English Abstract, Journal Article]
- Rev Med Chil 2014 Jun; 142(6):696-701.
Respiratory viral infections (RVi) can be associated with a wide range of clinical manifestations.To investigate the frequency and clinical manifestations of RVi among adult patients during winter hospitalizations.All patients admitted to the hospital with flu like disease and those with fever or exacerbation of any underlying disease during hospitalization without an evident cause, were prospectively enrolled. A direct immunofluorescence (DIF) of nasopharyngeal aspirate for influenza A (IA) and B, parainfluenza 1, 2 and 3, adenovirus, respiratory syncytial virus (RSV) and metapneumovirus, was performed. Epidemiological and clinical data were recorded.Between May and September 2012, 975 adults were admitted to the Internal Medicine Unit of Puerto Montt Hospital and in 128 (13%) patients, DIF was carried out. DIF was positive in 44 patients (34%) aged 65 ± 20 years, 68.2% females, corresponding to 4.5% of total hospitalizations. Eighty six percent of the latter had at least one co-morbidity, mainly asthma and chronic respiratory diseases in 34.1%, diabetes in 29.5%, cardiac problems in 25% and congestive heart failure in 20.5%. The most common RVi were RSV (n = 21, 48%) and IA (n = 17, 39%). Six patients had a nosocomial RVi. Patients infected with IA had a significantly higher frequency of fever and bronchial hyper reactivity than those infected with RSV. RVi were associated with exacerbation of underlying disease in 62% of cases and pneumonia in 27%. Two patients had a viral pericarditis.RVi are an important cause of adult morbidity and their detection should be routine in adult patients hospitalized during winter.
- Risk factors of prolonged hospital stay in children with viral severe acute respiratory infections. [Journal Article]
- J Infect Dev Ctries 2014; 8(10):1285-93.
Severe acute lower respiratory infections (SARIs) are one of the major causes of morbidity and mortality in young children, especially in developing countries. The present study focused on detection of risk factors for prolonged hospital stays among children with viral SARIs.A sentinel surveillance study was conducted at Cairo University Hospital (CUH) between February 2010 and May 2011. Nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected from all children admitted with SARIs. Viruses were identified using reverse transcription polymerase chain reaction (RT-PCR).Out of 1,046 children, 380 (36%) were positive for one or more viruses; these included respiratory syncytial virus (RSV) (22.9%), adenovirus (6.2%), parainfluenza viruses (PIVs1-3) (5.1%), human metapneumovirus (HMPV) (4.5%), influenza A (1.4%), and influenza B (0.6%). Viral etiology was mainly detected in children under one year of age (88.9%). Prolonged length of stay was independently associated with the presence of cyanosis and underlying chronic illness (OR 7.4, CI: 1.8-30.32 [p = 0.005], OR 2.5, CI: 1.36-4.64 [p = 0.004], respectively). Virus type did not affect the length of hospital stay (p > 0.05). Oxygen therapy was required in 91% of the patients. A total of 43 patients (11.6%) required intensive care admission. Twenty-one patients (5.5%) died, and 15 of them (71.4%) had an underlying chronic illness.The study demonstrated the important burden of respiratory viruses as a cause of SARI in hospitalized children in a tertiary Egyptian hospital. Cyanosis and underlying chronic illness were significantly associated with prolonged length of stay.
- Accurate identification of neutralizing antibodies to adenovirus Ad36, -a putative contributor of obesity in humans. [JOURNAL ARTICLE]
- J Diabetes Complications 2014 Sep 16.
In children and adults, human adenovirus serotype 36 (Ad36) is linked with increased adiposity, and important metabolic alterations. Since this property is not shared by many other human adenovirus serotypes, it is imperative to specifically identify exposure to Ad36. Although serum neutralization assay (SNA) is the gold standard to specifically detect neutralizing antibodies (NA) to Ad36, it requires 2-weeks to complete and considerable training to interpret the results. Whereas, an enzyme-immuno assay (EIA) may provide a quicker and objective determination.Evaluate the accuracy of commercially available EIA kits to detect NA to Ad36. Modify SNA to reduce time and increase objectivity.Sera of 15 seropositive or 16 seronegative subjects confirmed by SNA were used to test: 1) reproducibility of SNA to detect Ad36 exposure, by repeating assays twice; 2) an EIA that detects antibodies to all human adenovirus serotypes (NS-EIA) (Abcam-108705); 3) an EIA supposedly specific for Ad36 antibody (Ad36-EIA) (MyBioSource,#MBS705802), and 4) the concordance of SNA with a novel combination of SNA and immune-staining (SN-IS) kit (Cell BioLabs,#VPK-111).The SNA showed exact reproducibility. NS-EIA detected adenovirus antibodies in 94% samples, confirming the non-specificity of the assay for Ad36 serotype. All seronegative samples (as determined by SNA) were false positive by Ad36-EIA. In 97% samples, SN-IS showed fidelity with Ad36-antibody status as determined by SNA.The available EIA kits are not specific for detecting NA to Ad36. The modified SNA with immune-staining reduces assay time and increases accuracy of detecting by reducing subjectivity.
- The IgCAMs CAR, BT-IgSF, and CLMP: structure, function, and diseases. [Journal Article, Research Support, Non-U.S. Gov't, Review]
- Adv Neurobiol 2014.:21-45.
The coxsackie-adenovirus receptor (CAR) is the prototype of a small subfamily of IgCAMs composed of CAR itself, CLMP, BT-IgSF, ESAM, CTX, and A33. These six proteins are composed of one V-set and one C2-set Ig domains and a single transmembrane helix followed by a cytoplasmic stretch. They are localized in several tissues and organs and--except for ESAM, CTX, and A33--are expressed in the developing brain. CAR becomes downregulated at early postnatal stages and is absent from the adult brain. CAR, CLMP, and BT-IgSF mediate homotypic aggregation. Interestingly, cell adhesion experiments, binding studies, and crystallographic investigations on the extracellular domain reveal a flexible ectodomain for CAR that mediates homophilic and heterophilic binding. CAR has been extensively investigated in the context of gene therapy and diseases, while research on BT-IgSF and CLMP is at an early stage. Several mouse models as well as studies on patient tissues revealed an essential role for CAR in (1) the development of cardiac, renal, lymphatic, and intestinal tissue; (2) muscle pathology, remodeling, and regeneration; (3) tumor genesis/suppression and metastatic progression; and (4) in virus-mediated infections and gene therapy. Although the in vivo function of CAR in the brain has not been solved its developmentally regulated expression pattern in the brain as well as its function as CAM suggests that CAR might be implicated in neuronal network formation.
- Comparison of the FilmArray assay and in-house real-time PCR for detection of respiratory infection. [JOURNAL ARTICLE]
- Scand J Infect Dis 2014 Oct 7.:1-5.
Recently, molecular methods capable of detecting almost all microbial agents that may cause acute respiratory infection have been introduced. The FilmArray Respiratory Panel assay, which integrates nucleic acid extraction, nested amplification and detection in a reaction pouch preloaded with all reagents required for detection of 17 viruses and 3 bacteria, was compared with an in-house real-time PCR that detects these agents in 8 parallel amplifications. When 128 clinical samples representing 18 of these agents were analysed by both assays the agreement was excellent, with kappa values ranging between 0.54 and 1.0. Discordances were mainly observed for adenovirus, but not when version 1.7 of FilmArray was used. The results show that these assays detect a wide range of pathogens with similar performance. FilmArray provides results after approximately 1 h, including ≈ 5 min hands-on time, and does not require advanced equipment or expertise in molecular diagnostics, making it a useful point-of-care-test for acute respiratory infections.
- [Construction and immunological responses of recombinant adenovirus containing Epstein-Barr nuclear antigen 1 in mice]. [English Abstract, Journal Article, Research Support, Non-U.S. Gov't]
- Bing Du Xue Bao 2014 Jul; 30(4):429-35.
This study aimed to construct recombinant adenovirus expressing Epstein-Barr nuclear antigen 1 (EBNA1) against nasopharyngeal carcinoma (NPC). The C-terminal region fragment of the ebna1 gene of Epstein-Barr virus was amplified from the standard strain B95-8 by polymerase chain reaction (PCR). The gene fragment was inserted into the pDC316 shuttle plasmid using the EcoRI and BgIII restriction enzyme sites. The pDC316-ebna1 shuttle plasmid and pBHG helper plasmid were cotransfected into HEK293 cells after sequencing. The soluble protein was extracted from HEK293 cells, which caused apparent cytopathic effects. The transcription and expression of the ebna1 gene were confirmed using flow cytometry and Western blotting. rAd-ebna1 titers were measured by the TCID50. rAd-ebna1 was injected into BALB/c mice at a dose of 2 x 10(8) VP per mouse, EBNA1 epitope-specific responses were measured at 1st, 2nd, 4th and 8th weeks post-immunization. The target fragment of ebna1 (939 bp) was obtained by PCR, and was in consensus with the sequence from the standard strain B95-8. Cytopathic effects were observed after the pDC316-ebna1 shuttle plasmid and pBHG helper plasmid were cotransfected into HEK293 cells. rAd-ebna1 was successfully recombined in HEK293 cells. EBNA1 protein was detected in HEK293 cells, rAd-ebna1 titers reached 10(8) TCID50/mL. Specific responses to CD4+ epitopes of EBNA1 were detected in the immunized mice. In conclusion, rAd-ebna1 was successfully constructed and induced specific responses to CD4+ epitopes of EBNA1 in immunized mice.