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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenovirus infection after stem cell transplantation is a significant cause of morbidity and mortality, especially in children. A robust T-cell response induced by dendritic cells (DC) is crucial for clearing the virus, suggesting their pivotal role for the response to human adenoviruses (HAdV). Despite the widespread use of adenoviral vectors, the properties and kinetics of HAdV infection of DC have not been addressed yet. We show that a recent clinical HAdV, subgenus C/serotype 2 (strain BB2000-61), infects cells of the myeloid lineage. Infected DC produce early and late viral antigens and show an altered expression of surface markers. Infection of monocytes renders them refractory to differentiation into DC. Additionally, HAdV-infected DC are strong stimulators of CD8+ T cells. In summary, HAdV seems to manipulate the immune response by infection of DC and possibly uses the infection of monocytes as a means to escape recognition by T cells.
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PMID:Dendritic cells are susceptible to infection with wild-type adenovirus, inducing a differentiation arrest in precursor cells and inducing a strong T-cell stimulation. 2003 5

EBV-associated nasopharyngeal cancer (NPC) occurs with high frequency in China and is a major cause of morbidity and mortality. To explore the potential use of adenovirus-mediated tumor suppressor p53 gene therapy In NPC, we first examined the in vitro effects of p53 introduced into the NPC cell lines RPMI 2650, Fadu and Detroit 562. p21(WAF1/CIP1) induction by chemotherapy was used as a functional assay which revealed that RPMI 2650 expresses wild-type p53 whereas Fadu and Detroit 562 encode mutant p53. Infection with p53-expressing adenovirus (Ad-p53) induced apoptosis and inhibited cell growth in all three NPC cell lines, regardless of the endogenous p53 status. Adenovirus infectivity was greatest in RPMI 2650 cells, with 100% of the cells expressing beta-galactosidase following Ad-LacZ infection using an MOI of 100, as compared to 20-30% infectivity with the other NPC lines. Using RPMI 2650 cells injected into nude mice, we developed an animal model for nasopharyngeal cancer. Established tumors (0.6-0.8 cm) were injected with 5x10(9) PFU Ad-LacZ, Ad-p53 or PBS in a 100 mu l volume. We found evidence for in vivo expression of beta-galactosidase or p53 and p21 up to two weeks following Ad-LacZ or Ad-p53 virus injection respectively. Objective regression of tumor size was observed at two weeks in 4/6 Ad-p53-treated tumors, but not in Ad-LacZ or PBS-treated tumors. The results provide an animal model for human nasopharyngeal cancer, and indicate a potential use of p53 in its therapy in vivo.
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PMID:Adenovirus-mediated p53 gene therapy in nasopharyngeal cancer. 2152 3

Adenovirus often causes respiratory infection in immunocompromised patients, but relevant attachment receptors have largely not been defined. We show that the antiviral protein bovine lactoferrin enhances infection of monocyte-derived dendritic cells (MDDC) by adenovirus species C serotype 2 (2C) isolates. Under the same conditions infection of MDDC by human( )cytomegalovirus was reduced. Adenoviral infection was prominently enhanced by bovine but not human lactoferrin, and was not prominently enhanced using blood monocyte-derived macrophages, suggesting that the relevant receptor is expressed on MDDC. Infection of MDDC in the presence of bovine lactoferrin was blocked by mannan, and an antibody to CD209/DC-SIGN but not isotype control or CD46 antibodies. Lastly, U937 macrophages ectopically expressing CD209/DC-SIGN, but not parental U937 cells, were efficiently infected by adenovirus 2C in the presence of bovine lactoferrin. These results may provide a tool, given the high efficiency of infection, to dissect responses by myeloid cells to clinical adenovirus isolates.
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PMID:CD209/DC-SIGN mediates efficient infection of monocyte-derived dendritic cells by clinical adenovirus 2C isolates in the presence of bovine lactoferrin. 2156 23

Adenovirus (AdV) is a common cause of respiratory illness in both children and adults. Respiratory symptoms can range from those of the common cold to severe pneumonia. Infection can also cause significant disease in the immunocompromised and among immunocompetent subjects in close quarters. Fortunately, infection with AdV in the normal host is generally mild. This is one reason why its initial use as a gene-therapy vector appeared to be so promising. Unfortunately, both innate and adaptive responses to the virus have limited the development of AdV vectors as a tool of gene therapy by increasing toxicity and limiting duration of transgene expression. This article will focus on the innate immune response to infection with wild-type AdV and exposure to AdV gene-therapy vectors. As much of the known information relates to the pulmonary inflammatory response, this organ system will be emphasized. This article will also discuss how that understanding has led to the creation of new vectors for use in gene therapy.
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PMID:Implications of the innate immune response to adenovirus and adenoviral vectors. 2173 57

Adenoviruses are currently used in a variety of bench and bedside applications. However, their employment in gene delivery to lymphocyte lineages is hampered by the lack of coxsackie virus and adenovirus receptor (CAR) on the cell surface. Exploitation of an alternative receptor on the surface of T lymphocytes can allow for utilization of adenovirus in a variety of T lymphocyte-based diseases and therapies. Here, we describe how resistance to infection can be overcome by the utilization of a bi-specific fusion protein, soluble CAR murine interleukin 2 (sCAR-mIL-2), that retargets adenovirus to the murine IL-2 receptor (IL-2R). Infection of a murine T-cell line, CTLL-2, with a sCAR-mIL-2/Adenovirus conjugate provided a ninefold increase in both green fluorescence protein-positive cells and luciferase expression. In addition, this increase in infection was also seen in isolated primary murine T lymphocytes. In this context, the sCAR-mIL-2 adapter provided a fourfold gene transduction increase in activated primary murine T lymphocytes. Our results show that recombinant sCAR-mIL-2 fusion protein promotes IL-2R-targeted gene transfer to murine T lymphocytes and that alternative targeting can abrogate their native resistance to infection.
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PMID:Augmented adenovirus transduction of murine T lymphocytes utilizing a bi-specific protein targeting murine interleukin 2 receptor. 2590 93

We evaluated the antitumor effect of a telomerase-specific replication-selective adenovirus (Telomelysin, OBP-301) for adenoid cystic carcinoma (ACC) in vitro and in vivo. Adenovirus E1 gene expression was controlled by human telomerase reverse transcription (hTERT). Infection of ACC cells by OBP-301 induced high E1A mRNA expression and subsequent oncolytic cell death in a dose-dependent manner. Using OBP-401 (TelomeScan), a genetically engineered adenovirus that carries the GFP gene under the control of the cytomegalovirus (CMV) promoter at the deleted E3 region of OBP-301, ACC cells expressed bright GFP fluorescence as early as 12 h after OBP-401 infection. The fluorescence intensity gradually increased in a time-dependent manner, followed by rapid cell death due to the cytopathic effect of OBP-401, as evidenced by the floating, highly light-refractive cells using phase-contrast microscopy. Effects of intratumorally injected OBP-401 against established Acc2 xenograft tumors were seen in BALB/c nu/nu mice. The levels of GFP expression following ex vivo infection of OBP-401 may be of value as a positive predictive marker for the outcome of telomerase-specific virotherapy. Our data clearly indicated that telomerase-specific oncolytic adenoviruses have significant therapeutic potential against human ACC in vitro and in vivo. These results suggest that treatment with OBP-301 and OBP-401 may improve the quality of life of oral cancer patients.
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PMID:Antitumor effects of telomerase-specific replication-selective oncolytic viruses for adenoid cystic carcinoma cell lines. 2406 18

X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1), a XIAP-binding protein, is a tumor suppressor gene. XAF1 was silent or expressed lowly in most human malignant tumors. However, the role of XAF1 in hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the effect of XAF1 on tumor growth and angiogenesis in hepatocellular cancer cells. Our results showed that XAF1 expression was lower in HCC cell lines SMMC-7721, Hep G2 and BEL-7404 and liver cancer tissues than that in paired non-cancer liver tissues. Adenovirus-mediated XAF1 expression (Ad5/F35-XAF1) significantly inhibited cell proliferation and induced apoptosis in HCC cells in dose- and time- dependent manners. Infection of Ad5/F35-XAF1 induced cleavage of caspase -3, -8, -9 and PARP in HCC cells. Furthermore, Ad5/F35-XAF1 treatment significantly suppressed tumor growth in a xenograft model of liver cancer cells. Western Blot and immunohistochemistry staining showed that Ad5/F35-XAF1 treatment suppressed expression of vascular endothelial growth factor (VEGF), which is associated with tumor angiogenesis, in cancer cells and xenograft tumor tissues. Moreover, Ad5/F35-XAF1 treatment prolonged the survival of tumor-bearing mice. Our results demonstrate that XAF1 inhibits tumor growth by inducing apoptosis and inhibiting tumor angiogenesis. XAF1 may be a promising target for liver cancer treatment.
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PMID:Tumor suppressor XAF1 induces apoptosis, inhibits angiogenesis and inhibits tumor growth in hepatocellular carcinoma. 2498 Aug 21

Adenoviruses are emerging as important viral pathogens in hematopoietic stem cell and solid organ transplant recipients, impacting morbidity, graft survival, and even mortality. The risk seems to be highest in allogeneic hematopoietic stem cell transplant recipients as well as heart, lung, and small bowel transplant recipients. Most of the adenovirus diseases develop in the first 6 months after transplantation, particularly in pediatric patients. Among abdominal organ recipients, small bowel grafts are most frequently affected, presumably due to the presence of a virus reservoir in the mucosa-associated lymphoid tissue. Management of these infections may be difficult and includes the reduction of immunosuppression, whenever possible, combined with antiviral therapy, if necessary. Therefore, an awareness of the pathology associated with such infections is important in order to allow early detection and specific treatment. We reviewed six transplant recipients (small bowel, kidney, and heart) with adenovirus graft involvement from two institutions. We sought to compare the diagnostic morphology and the clinical and laboratory findings. The histopathologic features of an adenovirus infection of the renal graft and one native kidney in a heart transplant recipient included a vaguely granulomatous mixed inflammatory infiltrate associated with rare cells showing a cytopathic effect (smudgy nuclei). A lymphocytic infiltrate, simulating T cell rejection, with admixture of eosinophils was also seen. In the small bowel grafts, there was a focal mixed inflammatory infiltrate with associated necrosis in addition to cytopathic effects. In the heart, allograft adenovirus infection was silent with no evidence of inflammatory changes. Immunohistochemical stain for adenovirus was positive in all grafts and in one native kidney. All patients were subsequently cleared of adenovirus infection, as evidenced by follow-up biopsies, with no loss of the grafts. Adenovirus infection can involve allografts as well as native organs in solid organ transplant recipients. Infection is associated with variable necrosis and acute inflammation, in addition to a rejection-like infiltrate. Hematuria in non-renal solid organ transplant recipients may be associated with adenovirus nephritis and clinically silent graft involvement. Prompt diagnosis (aided by immunohistochemistry (IHC) and serology), with specific treatment, can prevent graft loss.
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PMID:Adenovirus disease in six small bowel, kidney and heart transplant recipients; pathology and clinical outcome. 2637 31

Infection by enveloped coronaviruses (CoVs) initiates with viral spike (S) proteins binding to cellular receptors, and is followed by proteolytic cleavage of receptor-bound S proteins, which prompts S protein-mediated virus-cell membrane fusion. Infection therefore requires close proximity of receptors and proteases. We considered whether tetraspanins, scaffolding proteins known to facilitate CoV infections, hold receptors and proteases together on cell membranes. Using knockout cell lines, we found that the tetraspanin CD9, but not the tetraspanin CD81, formed cell-surface complexes of dipeptidyl peptidase 4 (DPP4), the MERS-CoV receptor, and the type II transmembrane serine protease (TTSP) member TMPRSS2, a CoV-activating protease. This CD9-facilitated condensation of receptors and proteases allowed MERS-CoV pseudoviruses to enter cells rapidly and efficiently. Without CD9, MERS-CoV viruses were not activated by TTSPs, and they trafficked into endosomes to be cleaved much later and less efficiently by cathepsins. Thus, we identified DPP4:CD9:TTSP as the protein complexes necessary for early, efficient MERS-CoV entry. To evaluate the importance of these complexes in an in vivo CoV infection model, we used recombinant Adenovirus 5 (rAd5) vectors to express human DPP4 in mouse lungs, thereby sensitizing the animals to MERS-CoV infection. When the rAd5-hDPP4 vectors co-expressed small RNAs silencing Cd9 or Tmprss2, the animals were significantly less susceptible, indicating that CD9 and TMPRSS2 facilitated robust in vivo MERS-CoV infection of mouse lungs. Furthermore, the S proteins of virulent mouse-adapted MERS-CoVs acquired a CD9-dependent cell entry character, suggesting that CD9 is a selective agent in the evolution of CoV virulence.
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PMID:The tetraspanin CD9 facilitates MERS-coronavirus entry by scaffolding host cell receptors and proteases. 2875 49

Infectious diarrhea is endemic in most developing countries. We aimed to investigate the protozoan, viral, and bacterial causes of acute diarrhea in Taif, Saudi Arabia. A cross-sectional prospective 1-year study was conducted on 163 diarrheal patients of various ages. Stool samples were collected, 1 per patient, and tested for 3 protozoa, 3 viruses, and 9 bacteria with the Luminex Gastrointestinal Pathogen Panel. Overall, 53.4% (87/163) of samples were positives (20.8% protozoa, 19.6% viruses, 2.8% bacteria, and 9.8% mixed). Rotavirus (19.6%), Giardia duodenalis (16.5%), and Cryptosporidium spp. (8.5%) were the mostly detected pathogens. Adenovirus 40/41 (4.2%), Salmonella (3%), Shiga toxin-producing Escherichia coli (3%), and Entamoeba histolytica (2.4%) were also detected. Norovirus GI/II, Vibrio cholerae, Yersinia enterocolitica, and Clostridium difficile toxin A/B were not detected in any patients. All pathogens were involved in coinfections except E. histolytica. Giardia (5.5%) and rotavirus (3%) were the most commonly detected in co-infections. Enterotoxigenic E. coli (2.4%), Campylobacter spp. (2.4%), E. coli 0157 (1.8%), and Shigella spp. (1.2%) were detected in patients only as co-infections. Infections were more in children 0-4 years, less in adults <40 years, and least >40 years, with statistically significant differences in risk across age groups observed with rotavirus (P<0.001), Giardia (P=0.006), and Cryptosporidium (P=0.036) infections. Lastly, infections were not significantly more in the spring. This report demonstrates the high burden of various enteropathogens in the setting. Further studies are needed to define the impact of these findings on the clinical course of the disease.
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PMID:High Frequency of Enteric Protozoan, Viral, and Bacterial Potential Pathogens in Community-Acquired Acute Diarrheal Episodes: Evidence Based on Results of Luminex Gastrointestinal Pathogen Panel Assay. 2910 66


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