Post translational modifications in adenovirus type 2

Lind, Sara Bergström; Artemenko, Konstantin A.; Elfineh, Lioudmila; Zhao, Yang; Bergquist, Jonas; Pettersson, Ulf

doi:10.1016/j.virol.2013.08.033

Cited by 20 publications

(23 citation statements)

References 28 publications

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“…Once expressed, pIII binds with four other pIII macromolecules to form the penton base, which is located at each of the 12 vertexes of the icosahedral Ad capsid [68]. Ad serotype 2 encoded pIII peptide (98.6% similarity to Ad5 by BLAST peptide analysis) was shown to be the most highly phosphorylated peptide in the Ad2 phosphatome with 12 total phosphorylation sites: one tyrosine, one threonine and 10 serine residues [69]. This truncated form of pIII expressed by AdUV may form smaller pIII pentamers (penton) with fewer phosphorylation sites.…”

Section: Resultsmentioning

confidence: 99%

Adenovirus with DNA Packaging Gene Mutations Increased Virus Release

Wechman

Rao

McMasters

et al. 2016

Viruses

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Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies using E1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of targeting other viral genes for manipulation. To improve the therapeutic efficacy of oncolytic Ads, we treated the entire Ad genome repeatedly with UV-light and have isolated AdUV which efficiently lyses cancer cells as reported previously (Wechman, S. L. et al. Development of an Oncolytic Adenovirus with Enhanced Spread Ability through Repeated UV Irradiation and Cancer Selection. Viruses 2016, 8, 6). In this report, we show that no mutations were observed in the early genes (E1 or E4) of AdUV while several mutations were observed within the Ad late genes which have structural or viral DNA packaging functions. This study also reported the increased release of AdUV from cancer cells. In this study, we found that AdUV inhibits tumor growth following intratumoral injection. These results indicate the potentially significant role of the viral late genes, in particular the DNA packaging genes, to enhance Ad oncolysis.

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Section: Resultsmentioning

confidence: 99%

Adenovirus with DNA Packaging Gene Mutations Increased Virus Release

Wechman

Rao

McMasters

et al. 2016

Viruses

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“…The latter was done based on knowledge of basic theory of peptide fragmentation, as well as considering possible misinterpretations (description of the details can be found in Bergström Lind et al . ).…”

Section: Methodsmentioning

confidence: 97%

Time course analysis of mechanical ventilation‐induced diaphragm contractile muscle dysfunction in the rat

Corpeno

Dworkin

Cacciani

et al. 2014

The Journal of Physiology

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Key pointsr Weaning from mechanical ventilation (MV) of long-term intensive care unit (ICU) patients is delayed by impaired respiratory muscle function; however, the mechanisms that cause the impairment are not fully understood.r A novel experimental rat ICU model was used for time-resolved analyses (6 h to 2 weeks) of the effects of MV on diaphragm muscle fibre structure and function, and on gene and protein expression.r A prompt and progressive decline of diaphragm muscle fibre function, preceding atrophy, occurred with MV, and at the end of 2 weeks residual diaphragm muscle fibre function was <15% of control levels.r Cellular and subcellular analyses indicated that oxidative stress-triggered protein modifications had significantly diminished diaphragm muscle fibre function.r The novel finding that activation of proteolytic pathways and regulation of contractile protein synthesis were different in diaphragm and limb muscles has direct implications for the design of muscle-specific intervention strategies.Abstract Controlled mechanical ventilation (CMV) plays a key role in triggering the impaired diaphragm muscle function and the concomitant delayed weaning from the respirator in critically ill intensive care unit (ICU) patients. To date, experimental and clinical studies have primarily focused on early effects on the diaphragm by CMV, or at specific time points. To improve our understanding of the mechanisms underlying the impaired diaphragm muscle function in response to mechanical ventilation, we have performed time-resolved analyses between 6 h and 14 days using an experimental rat ICU model allowing detailed studies of the diaphragm in response to long-term CMV. A rapid and early decline in maximum muscle fibre force and preceding muscle fibre atrophy was observed in the diaphragm in response to CMV, resulting in an 85% reduction in residual diaphragm fibre function after 9-14 days of CMV. A modest loss of contractile proteins was observed and linked to an early activation of the ubiquitin proteasome pathway, myosin:actin ratios were not affected and the transcriptional regulation of myosin isoforms did not show any dramatic changes during the observation period. Furthermore, small angle X-ray diffraction analyses demonstrate that myosin can bind to actin in an ATP-dependent manner even after 9-14 days of exposure to CMV. Thus, quantitative changes in muscle fibre size and contractile proteins are not the dominating factors underlying the dramatic decline in diaphragm muscle function in response to CMV, in contrast to earlier observations in limb muscles. The observed early loss of subsarcolemmal neuronal nitric oxide synthase activity, onset of oxidative stress, intracellular lipid accumulation and post-translational protein modifications strongly argue for significant qualitative changes in contractile proteins causing the severely impaired residual function in diaphragm fibres after long-term mechanical ventilation. For the first time, the present study demonstrates novel changes in the diaphragm struct...

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“…Third, all remaining peptides were verified, that is, their mass spectra were manually checked for PTM confirmation. The latter was done based on knowledge of basic theory of peptide fragmentation, as well as considering possible misinterpretations (description of the details can be found in). Only fully confirmed (with unambiguous MS/MS spectra) PTMs were reported in the results.…”

Section: Methodsmentioning

confidence: 99%

Chaperone co‐inducer BGP‐15 mitigates early contractile dysfunction of the soleus muscle in a rat ICU model

Cacciani

Salah

et al. 2019

Acta Physiologica

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Aim Critical illness myopathy (CIM) represents a common consequence of modern intensive care, negatively impacting patient health and significantly increasing health care costs; however, there is no treatment available apart from symptomatic and supportive interventions. The chaperone co‐inducer BGP‐15 has previously been shown to have a positive effect on the diaphragm in rats exposed to the intensive care unit (ICU) condition. In this study, we aim to explore the effects of BGP‐15 on a limb muscle (soleus muscle) in response to the ICU condition. Methods Sprague‐Dawley rats were subjected to the ICU condition for 5, 8 and 10 days and compared with untreated sham‐operated controls. Results BGP‐15 significantly improved soleus muscle fibre force after 5 days exposure to the ICU condition. This improvement was associated with the protection of myosin from post‐translational myosin modifications, improved mitochondrial structure/biogenesis and reduced the expression of MuRF1 and Fbxo31 E3 ligases. At longer durations (8 and 10 days), BGP‐15 had no protective effect when the hallmark of CIM had become manifest, that is, preferential loss of myosin. Unrelated to the effects on skeletal muscle, BGP‐15 had a strong positive effect on survival compared with untreated animals. Conclusions BGP‐15 treatment improved soleus muscle fibre and motor protein function after 5 days exposure to the ICU condition, but not at longer durations (8 and 10 days) when the preferential loss of myosin was manifest. Thus, long‐term CIM interventions targeting limb muscle fibre/myosin force generation capacity need to consider both the post‐translational modifications and the loss of myosin.

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Post translational modifications in adenovirus type 2

Cited by 20 publications

References 28 publications

Adenovirus with DNA Packaging Gene Mutations Increased Virus Release

Adenovirus with DNA Packaging Gene Mutations Increased Virus Release

Time course analysis of mechanical ventilation‐induced diaphragm contractile muscle dysfunction in the rat

Chaperone co‐inducer BGP‐15 mitigates early contractile dysfunction of the soleus muscle in a rat ICU model

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