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Adenovirus infections [keywords]
- The sweet spot: defining virus-sialic acid interactions. [JOURNAL ARTICLE]
- Nat Rev Microbiol 2014 Sep 29.
Viral infections are initiated by attachment of the virus to host cell surface receptors, including sialic acid-containing glycans. It is now possible to rapidly identify specific glycan receptors using glycan array screening, to define atomic-level structures of virus-glycan complexes and to alter the glycan-binding site to determine the function of glycan engagement in viral disease. This Review highlights general principles of virus-glycan interactions and provides specific examples of sialic acid binding by viruses with stalk-like attachment proteins, including influenza virus, reovirus, adenovirus and rotavirus. Understanding virus-glycan interactions is essential to combating viral infections and designing improved viral vectors for therapeutic applications.
- Post-infectious bronchiolitis obliterans in children: a review of 42 cases. [JOURNAL ARTICLE]
- BMC Pediatr 2014 Sep 25; 14(1):238.
This study aimed to describe the clinical characteristics, radiological features and outcomes of 42 children with post-infectious bronchiolitis obliterans (PIBO).Forty-two children diagnosed with PIBO were prospectively studied at the First Hospital of Jilin University in northern China between January, 2008 and January, 2013. Their clinical characteristics, lung high resolution computed tomography (HRCT) findings and pulmonary function tests were reported.In children with PIBO, adenovirus was the most common etiologic agent (21/42), followed by Mycoplasma pneumoniae (M. pneumoniae). All of the patients presented with repeated wheezing and tachypnea. In addition, 22 patients required intensive management, while six patients required home oxygen therapy. HRCT findings were consistent with the PIBO diagnosis in all of the patients. Pulmonary function testing was useful in evaluating therapeutic responses. Systemic steroids combined with azithromycin were effective for PIBO treatment.Severe adenovirus bronchiolitis and M. pneumoniae infections have a higher risk of development for PIBO. HRCT and pulmonary function testing are useful in the diagnosis of PIBO. The degree of airway obstruction did not differ significantly between adenovirus and M. pneumoniae. A combination of steroids and azithromycin offers some benefit in treating these patients.
- Viral infection in placenta relevant cells - a morphological and immunohistochemical cell culture study. [JOURNAL ARTICLE]
- APMIS 2014 Sep 22.
Viral infections in pregnancy are known to cause fetal malformation, growth restriction, and even fetal death. Macroscopic placental examination usually shows slight and unspecific changes. Histology may show secondary, non-specific tissue reaction, i.e. villitis with lymphocytic invasion. Primary specific morphology characteristics are known for some virus, like cytomegalovirus, parvovirus, and herpes simplex, however many viral infections show non-specific changes. Placenta relevant cells as human first trimester trophoblasts HTR8/SVneo, primary human umbilical vein endothelial cells (HUVEC), and primary human embryonic fibroblasts were examined following infection with commonly occurring virus like adenovirus and enterovirus. Morphology in routine stained sections and virus-specific immunostains were studied 4, 8, 24, 48, 72 h after infection. Nuclear enlargement was seen in the infected cells. A specific diagnosis of adenovirus or enterovirus infection, however, was not possible without specific immunostains.
- An outbreak of acute respiratory disease in China caused by human adenovirus type 55 in a physical training facility. [JOURNAL ARTICLE]
- Int J Infect Dis 2014 Sep 15.
To investigate the cause of an acute respiratory tract infection (ARTI) outbreak.Thirty-eight clinical samples were collected from 19 patients in an ARTI outbreak that occurred in a physical training facility in January 2013; patient demographic information was also collected. In addition, 60 influenza virus-negative samples from febrile respiratory patients were collected from the same community at the same time to determine whether these were the same infections. Multiplex PCR (multi-PCR) was used to detect the possible pathogen in these samples. All human adenovirus (HAdV)-positive samples were inoculated onto Hep-2 cells for isolation. HAdV isolates were typed by hexon gene, fiber gene, and whole genome sequencing using primers designed in-house and compared to different type/serotype HAdVs downloaded from GenBank. Phylogenetic analysis was used to determine the type of the HAdV.Of the 38 samples, 34 from 17 cases were HAdV-positive; two of them were co-infected, one with respiratory syncytial virus A and the other with human rhinovirus. The hexon gene open reading frame (ORF; 2841 nucleotides (nt)) and fiber gene ORF (978 nt) were obtained from four HAdV strains (TJ-2013-92, TJ-2013-94, TJ-2013-100, TJ-2013-122) from three upper respiratory infection cases and one pneumonia case. They were all completely identical. One HAdV isolate, TJ-2013-90, was selected for whole genome sequencing; 34 238 nt were obtained. Phylogenetic analysis showed the whole genome of TJ-2013-90 to be clustered together with HAdV-B55/HAdV-B11a. Three of 60 influenza virus-negative specimens were HAdV-positive, but hexon and fiber gene analysis showed that they were grouped in different branches to the HAdV isolates from this outbreak.The cause of this ARTI outbreak was HAdV-B55. This was another outbreak caused by this re-emerging virus. Continuous surveillance of respiratory adenovirus is necessary for disease control.
- Ganciclovir Inhibits Human Adenovirus Replication and Pathogenicity in Permissive Immunosuppressed Syrian Hamsters. [JOURNAL ARTICLE]
- Antimicrob Agents Chemother 2014 Sep 15.
Adenovirus infections of immunocompromised patients can develop into deadly multi-organ or systemic disease. The virus is especially threatening for pediatric allogeneic hematopoietic stem cell transplant recipients; according to some studies, 10% or more of these patients succumb to disease resulting from adenovirus infection. At present, there is no drug approved for treatment or prevention of adenovirus infections. Compounds that are approved to treat other virus infections are used off-label to combat adenovirus, but only anecdotal evidence exists as to the efficacy of these drugs. Ganciclovir, a drug approved for the treatment of herpesvirus infection, was reported previously to be effective against human adenoviruses in vitro. To model adenovirus infections in immunocompromised humans, we examined ganciclovir's efficacy in immunosuppressed Syrian hamsters intravenously infected with type 5 human adenovirus (Ad5). This animal model is permissive for Ad5 replication, and develops symptoms similar to those seen in humans. We demonstrate that ganciclovir suppresses Ad5 replication in the liver of infected hamsters, and that it mitigates the consequences of Ad5 infections in these animals when administered prophylactically or therapeutically. We show that ganciclovir inhibits Ad5 DNA synthesis and late gene expression. The mechanism of action for the drug is not clear; preliminary data suggest that it exerts its anti-adenoviral effect by directly inhibiting the adenoviral DNA polymerase. While more extensive studies are required, we believe that ganciclovir is a promising drug candidate to treat adenovirus infections. Brincidofovir, a drug with proven activity against Ad5 was used as a positive control in the prophylactic experiment.
- The use of a multiplex real-time PCR assay for diagnosing acute respiratory viral infections in children attending an emergency unit. [JOURNAL ARTICLE]
- J Clin Virol 2014 Sep 3.
The use of a multiplex molecular technique to identify the etiological pathogen of respiratory viral infections might be a support as clinical signs are not characteristic.The aim of the study was to evaluate a multiplex molecular real-time assay for the routine diagnosis of respiratory viruses, to analyze the symptoms associated with the pathogens detected and to determine the spread of virus during the period.Respiratory samples were collected from children presenting with respiratory symptoms and attending the emergency unit during the 2010-2011 winter seasons. Samples were tested with the multiplex RespiFinder(®) 15 assay (PathoFinder™) which potentially detects 15 viruses.857 (88.7%) of the 966 samples collected from 914 children were positive for one (683 samples) or multiple viruses (174 samples). The most prevalent were the respiratory syncytial virus (39.5%) and the rhinovirus (24.4%). Influenza viruses were detected in 139 (14.4%) samples. Adenovirus was detected in 93 (9.6%) samples, coronaviruses in 88 (9.1%), metapneumovirus in 51 (5.3%) and parainfluenzae in 47 (4.9%). Rhinovirus (40%) was the most prevalent pathogen in upper respiratory tract infections while respiratory syncytial virus (49.9%) was the most prevalent in lower respiratory tract infections. Co-infections were associated with severe respiratory symptoms.The multiplex assay detected clinically important viruses in a single genomic test and thus will be useful for detecting several viruses causing respiratory tract disorders.
- Sheep lung segmental delivery strategy demonstrates adenovirus priming of local lung responses to bacterial LPS and the role of elafin as a response modulator. [Journal Article]
- PLoS One 2014; 9(9):e107590.
Viral lung infections increase susceptibility to subsequent bacterial infection. We questioned whether local lung administration of recombinant adenoviral vectors in the sheep would alter the susceptibility of the lung to subsequent challenge with bacterial lipopolysaccharide (LPS). We further questioned whether local lung expression of elafin, a locally produced alarm anti-LPS/anti-bacterial molecule, would modulate the challenge response. We established that adenoviral vector treatment primed the lung for an enhanced response to bacterial LPS. Whereas this local effect appeared to be independent of the transgene used (Ad-o-elafin or Ad-GFP), Ad-o-elafin treated sheep demonstrated a more profound lymphopenia in response to local lung administration of LPS. The local influence of elafin in modulating the response to LPS was restricted to maintaining neutrophil myeloperoxidase activity, and levels of alveolar macrophage and neutrophil phagocytosis at higher levels post-LPS. Adenoviral vector-bacterial synergism exists in the ovine lung and elafin expression modulates such synergism both locally and systemically.
- Symptomatic and asymptomatic respiratory viral infections in the first year of life: Association with acute otitis media development. [JOURNAL ARTICLE]
- Clin Infect Dis 2014 Sep 9.
Sensitive diagnostic assays have increased the detection of viruses in asymptomatic individuals. The clinical significance of asymptomatic respiratory viral infection in infants is unknown. High-throughput, quantitative PCR assays were used to detect 13 common respiratory viruses from nasopharyngeal specimens collected during 2028 visits from 362 infants followed from near birth up to 12 months of age. Specimens were collected at monthly interval (months 1-6 and month 9) and during upper respiratory tract infection (URI) episodes. Subjects were followed closely for acute otitis media (AOM) development. Viruses were detected in 76% of 394 URI specimens and 27% of asymptomatic monthly specimens. Rhinovirus was detected most often; multiple viruses were detected in 29% of the specimens. Generalized mixed model analyses associated symptoms with increasing age and female gender; detection of RSV, influenza, rhinovirus, metapneumovirus, and adenovirus were highly associated with symptoms. Increasing age was also associated with multiple virus detection. Overall, 403 asymptomatic viral infections in 237 infants were identified. Viral load was significantly higher in URI specimens than asymptomatic specimens but did not differentiate cases of URI with and without AOM complication. The rate of AOM complicating URI was 27%; no AOM occurred following asymptomatic viral infections. AOM development was associated with increasing age and infection with RSV, rhinovirus, enterovirus, adenovirus and bocavirus. Compared to symptomatic infection, asymptomatic viral infection in infants is associated with young age, male gender, low viral load, specific viruses and single virus detection. Asymptomatic viral infection did not result in AOM.
- Differential expression of THELPER 1 cytokines upon antigen stimulation predicts ex vivo proliferative potential and cytokine production of virus-specific T cells following re-stimulation. [JOURNAL ARTICLE]
- Transpl Infect Dis 2014 Sep 9.
Cytomegalovirus (CMV) and human adenovirus (ADV) infections are causes of morbidity after stem cell transplantation. Antigen (Ag)-specific T cells are essential for the control of viral infections. However, in vivo expansion potential of T-cell subpopulations is hardly predictable in humans. Furthermore, ex vivo identification of human T cells with repopulating capacity for adoptive T-cell transfer has been difficult.We analyzed Ag-specific T-cell populations, subdivided according to the expression of different THELPER- 1 (Th1) cytokines. Isolation by flow cytometry was based on interferon-gamma (IFN)-γ, interleukin (IL)-2, or tumor necrosis factor-alpha (TNF-α) secretion of T cells after ex vivo stimulation with the Ags hexon (for ADV) and pp65 (for CMV). Isolated T cells were expanded and examined for functional characteristics, expansion/differentiation potential, and naïve, effector memory, central memory, and late effector phenotypes.Isolation based on IFN-γ production provides a T-cell population with a mixture of early, central memory, and effector memory T cells, high expansion potential, and effective cytokine production. Selection of T cells with Ag-specific expression of IL-2 or TNF-α, however, results in a T-cell population with reduced proliferation and lower effector potential after expansion.We conclude that the exclusive secretion of IFN-γ in the human antiviral T-cell responses preferentially leads to higher repopulation capacities of antiviral T cells, compared to IL-2 or TNF-α secreting T-cell populations.
- Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals. [JOURNAL ARTICLE]
- Proc Natl Acad Sci U S A 2014 Sep 2.
Efficacy trials of adenovirus 5-vectored candidate HIV vaccines [recombinant Ad5 (rAd5)-HIV] were halted for futility due to lack of vaccine efficacy and unexpected excess HIV infections in the vaccine recipients. The potential immunologic basis for these observations is unclear. We comparatively evaluated the HIV susceptibility and phenotypes of human CD4 T cells specific to Ad5 and CMV, two viruses that have been used as HIV vaccine vectors. We show that Ad5-specific CD4 T cells, either induced by natural Ad5 exposure or expanded by rAd5 vaccination, are highly susceptible to HIV in vitro and are preferentially lost in HIV-infected individuals compared with CMV-specific CD4 T cells. Further investigation demonstrated that Ad5-specific CD4 T cells selectively display a proinflammatory Th17-like phenotype and express macrophage inflammatory protein 3α and α4β7 integrin, suggestive of gut mucosa homing potential of these cells. Analysis of HIV p24 and cytokine coexpression using flow cytometry revealed preferential infection of IL-17- and IL-2-producing, Ad5-specific CD4 T cells by HIV in vitro. Our data suggest a potential mechanism explaining the excess HIV infections in vaccine recipients after rAd5-HIV vaccination and highlight the importance of testing the HIV susceptibility of vaccine-generated, vector and insert-specific CD4 T cells in future HIV vaccine studies.