Adenoviruses: update on structure and function

Russell, W. C.

doi:10.1099/vir.0.003087-0

Cited by 344 publications

(289 citation statements)

References 248 publications

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“…In a considerable proportion of patients, Ads persist for a variable length of time after primary infection and may become latent (3,4), with members of species C (e.g., Ad2 or Ad5) being most often detected (3). Their successful propagation in vivo is facilitated by multiple strategies to evade the host immune response (1,5,6). Many of these immune evasion functions are encoded in the early transcription unit 3 (E3), which is not required for virus replication in tissue culture cells but is preserved in all human Ads (5,7).…”

mentioning

confidence: 99%

Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins

Sester

Koebernick

Owen

et al. 2009

The Journal of Immunology

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Successful establishment and persistence of adenovirus (Ad) infections are facilitated by immunosubversive functions encoded in the early transcription unit 3 (E3). The E3/19K protein has a dual role, preventing cell surface transport of MHC class I/HLA class I (MHC-I/HLA-I) Ags and the MHC-I–like molecules (MHC-I chain-related chain A and B [MICA/B]), thereby inhibiting both recognition by CD8 T cells and NK cells. Although some crucial functional elements in E3/19K have been identified, a systematic analysis of the functional importance of individual amino acids is missing. We now have substituted alanine for each of 21 aas in the luminal domain of Ad2 E3/19K conserved among Ads and investigated the effects on HLA-I downregulation by coimmunoprecipitation, pulse-chase analysis, and/or flow cytometry. Potential structural alterations were monitored using conformation-dependent E3/19K-specific mAbs. The results revealed that only a small number of mutations abrogated HLA-I complex formation (e.g., substitutions W52, M87, and W96). Mutants M87 and W96 were particularly interesting as they exhibited only minimal structural changes suggesting that these amino acids make direct contacts with HLA-I. The considerable number of substitutions with little functional defects implied that E3/19K may have additional cellular target molecules. Indeed, when assessing MICA/B cell-surface expression we found that mutation of T14 and M82 selectively compromised MICA/B downregulation with essentially no effect on HLA-I modulation. In general, downregulation of HLA-I was more severely affected than that of MICA/B; for example, substitutions W52, M87, and W96 essentially abrogated HLA-I modulation while largely retaining the ability to sequester MICA/B. Thus, distinct conserved amino acids seem preferentially important for a particular functional activity of E3/19K.

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confidence: 99%

Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins

Sester

Koebernick

Owen

et al. 2009

The Journal of Immunology

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“…The greater proliferation of fMSC is sufficient to explain the greater reduction in GFP positive cells resulting in a gradual dilution of the adenoviral genome as cell division occurs [20][21][22] . This is due to the fact that Ad transduction does not result in DNA integration into the host genome; therefore the delivered gene will be expressed only as long as the viral genome is present [11,18] . Osteogenic differentiation capacity was not affected by Ad transduction in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the permissiveness to gene delivery and the effect of genetic engineering on stemness in these young cells has not been extensively studied. Gene delivery to fMSCs may differ from adult (a) MSC due to immaturity of gene expression cellular pathways and cell surface receptors, such as the coxsackievirus adenovirus receptor required for adenoviral transduction [11] . To our knowledge, only two original research studies have evaluated gene delivery on fMSCs.…”

Section: Introductionmentioning

confidence: 99%

Fetal vs adult mesenchymal stem cells achieve greater gene expression, but less osteoinduction

Santiago-Torres

Lovasz

Bertone

2015

WJSC

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AIM:To investigate adenoviral transduction in mesenchymal stem cells (MSCs) and effects on stemness in vitro and function as a cell therapy in vivo . METHODS:Bone marrow-derived adult and fetal MSC were isolated from an equine source and expanded in monolayer tissue culture. Polyethylenimine (PEI)-mediated transfection of pcDNA3-eGFP or adenoviral transduction of green fluorescent protein (GFP) was evaluated in fetal MSCs. Adenoviral-mediated transduction was chosen for subsequent experiments. All experiments were carried out at least in triplicate unless otherwise noted. Outcome assessment was obtained by flow cytometry or immunohystochemistry and included transduction efficiency, cell viability, stemness (i.e. , cell proliferation, osteogenic and chondrogenic cell differentiation), and quantification of GFP expression. Fetal and adult MSCs were then transduced with an adenoviral vector containing the gene for the bone morphogenic protein 2 (BMP2). In vitro BMP2 expression was assessed by enzyme linked immunosorbent assay. In addition, MSC-mediated gene delivery of BMP2 was evaluated in vivo in an osteoinduction nude mouse quadriceps model. New bone formation was evaluated by microradiography and histology.RESULTS: PEI provided greater transfection and viability in fetal MSCs than other commercial chemical reagents. Adenoviral transduction efficiency was superior to PEI-mediated transfection of GFP in fetal MSCs (81.3% ± 1.3% vs 35.0% ± 1.6%, P < 0.05) and was similar in adult MSCs (78.1% ± 1.9%). Adenoviral transduction provided significantly greater expression of GFP in fetal than adult MSCs (7.4 ± 0.1 vs 4.4 ± 0.3 millions of mean fluorescence intensity units, P < 0.01) as well as significantly greater in vitro BMP2 expression (0.16 pg/cell-day vs 0.10 pg/cell-day, P < 0.01). Fraction of fetal MSC GFP positive cells decreased significantly faster than adult MSCs (1.15% ± 0.05% vs 11.4% ± 2.1% GFP positive at 2 wk post-transduction, P < 0.05). Cell proliferation and osteogenic differentiation in vitro Clinical Trials Studywere not affected by Ad transduction in both fetal and adult MSCs, but fetal MSCs had reduced chondrogenic differentiation in vitro when compared to adult (P < 0.01). Chondrogenic differentiation was also significantly reduced in Ad-GFP transduced cells (P < 0.05). Ad-BMP2 transduced adult MSCs induced new bone formation in more thighs than Ad-BMP2 transduced fetal MSCs (83% vs 17% of the six treated thighs per group, P < 0.05) and resulted in increased femur midshaft diameter due to greater extent of periosteal new bone (1.57 ± 0.35 mm vs 1.27 ± 0.08 mm, P < 0.05). CONCLUSION:Fetal MSCs may be genetically manipulated ex vivo with adenoviral vectors. Nonetheless, the abbreviated expression of the exogenous gene may limit their applications in vivo .

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“…Additional types continue to be identified and characterized using genomics and bioinformatics. Clinical manifestations are highly heterogeneous, ranging from upper and lower respiratory tract infections to gastroenteritis, pneumonia, urinary tract infection, conjunctivitis, hepatitis, myocarditis and encephalitis [88,89]. Adenoviruses can cause severe or life-threatening illness, particularly in immunocompromised patients, children and the elderly.…”

Section: Human Adenoviruses (Hadvs) Are Non-enveloped Icosahedral VImentioning

confidence: 99%

Emerging and potentially emerging viruses in water environments

Rosa

Fratini

Libera

et al. 2012

Annali Dell'Istituto Superiore Di Sanità

113

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Abstract. Among microorganisms, viruses are best fit to become emerging pathogens since they are able to adapt not only by mutation but also through recombination and reassortment and can thus become able to infect new hosts and to adjust to new environments. Enteric viruses are among the commonest and most hazardous waterborne pathogens, causing both sporadic and outbreak-related illness. The main health effect associated with enteric viruses is gastrointestinal illness, but they can also cause respiratory symptoms, conjunctivitis, hepatitis, central nervous system infections, and chronic diseases. Non-enteric viruses, such as respiratory and epitheliotrophic viruses are not considered waterborne, as they are not readily transmitted to water sources from infected individuals. The present review will focus on viral pathogens shown to be transmitted through water. It will also provide an overview of viruses that had not been a concern for waterborne transmission in the past, but that may represent potentially emerging waterborne pathogens due to their occurrence and persistence in water environments.Key words: viruses, waterborne, emerging, drinking water, recreational water. Riassunto (Infezioni emergenti e potenzialmente emergenti in ambienti acquatici).I virus sono tra i principali agenti di infezioni emergenti, in quanto sono in grado di acquisire nuove caratteristiche biologiche attraverso fenomeni di mutazione, ricombinazione e riassortimento genico, adattandosi così a nuovi ospiti e nuove nicchie ecologiche. I virus enterici sono tra le principali cause di malattie infettive di origine idrica, che possono manifestarsi come casi sporadici o cluster epidemici. Le manifestazioni cliniche più comuni sono le gastroenteriti; tuttavia i virus enterici sono in grado di causare anche sintomi respiratori, congiuntiviti, epatiti, infezioni del sistema nervoso centrale e malattie croniche. La presente rassegna fornisce una panoramica dei virus enterici tradizionalmente associati alle malattie idrotrasmesse; mostra inoltre dati epidemiologici su alcuni gruppi di virus che non sono stati associati a malattie idrodiffuse in passato (inclusi virus respiratori ed epiteliotropici), ma che possono rappresentare nuovi patogeni emergenti a causa della loro presenza e persistenza in ambienti acquatici.Parole chiave: virus, malattie idrotrasmesse, patogeni emergenti, acque potabili, acque ricreative.

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Adenoviruses: update on structure and function

Cited by 344 publications

References 248 publications

Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins

Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins

Fetal vs adult mesenchymal stem cells achieve greater gene expression, but less osteoinduction

Emerging and potentially emerging viruses in water environments

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