scholarly journals Identification of Lysine Acetylation Sites on MERS-CoV Replicase pp1ab

2020 ◽  
Vol 19 (8) ◽  
pp. 1303-1309 ◽  
Author(s):  
Lin Zhu ◽  
Sin-Yee Fung ◽  
Guangshan Xie ◽  
Lok-Yin Roy Wong ◽  
Dong-Yan Jin ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Bioinformatic Analysis ◽  
Hek293 Cells ◽  
Lysine Acetylation ◽  
Protein Acetylation ◽  
Conservation Level ◽  
Life Threatening ◽  
Infected Cells ◽  
Orbitrap Analysis ◽  
First Time

MERS is a life-threatening disease and MERS-CoV has the potential to cause the next pandemic. Protein acetylation is known to play a crucial role in host response to viral infection. Acetylation of viral proteins encoded by other RNA viruses have been reported to affect viral replication. It is therefore of interest to see whether MERS-CoV proteins are also acetylated. Viral proteins obtained from infected cells were trypsin-digested into peptides. Acetylated peptides were enriched by immunoprecipitation and subject to nano-LC-Orbitrap analysis. Bioinformatic analysis was performed to assess the conservation level of identified acetylation sites and to predict the upstream regulatory factors. A total of 12 acetylation sites were identified from 7 peptides, which all belong to the replicase polyprotein pp1ab. All identified acetylation sites were found to be highly conserved across MERS-CoV sequences in NCBI database. Upstream factors, including deacetylases of the SIRT1 and HDAC families as well as acetyltransferases of the TIP60 family, were predicted to be responsible for regulating the acetylation events identified. Western blotting confirms that acetylation events indeed occur on pp1ab protein by expressing NSP4 in HEK293 cells. Acetylation events on MERS-CoV viral protein pp1ab were identified for the first time, which indicate that MERS-CoV might use the host acetylation machinery to regulate its enzyme activity and to achieve optimal replication. Upstream factors were predicted, which might facilitate further analysis of the regulatory mechanism of MERS-CoV replication.

scholarly journals Discovery of Structurally Diverse Small-Molecule Compounds with Broad Antiviral Activity against Enteroviruses

2015 ◽  
Vol 60 (3) ◽  
pp. 1615-1626 ◽  
Author(s):  
Jun Zuo ◽  
Steve Kye ◽  
Kevin K. Quinn ◽  
Paige Cooper ◽  
Robert Damoiseaux ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Internal Ribosome Entry Site ◽  
Viral Proteins ◽  
Molecular Screening ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Viral Proteases ◽  
Life Threatening ◽  
Infected Cells ◽  
Resistant Mutants

Antiviral drugs do not currently exist for the treatment of enterovirus infections, which are often severe and potentially life-threatening. We conducted high-throughput molecular screening and identified a structurally diverse set of compounds that inhibit the replication of coxsackievirus B3, a commonly encountered enterovirus. These compounds did not interfere with the function of the viral internal ribosome entry site or with the activity of the viral proteases, but they did drastically reduce the synthesis of viral RNA and viral proteins in infected cells. Sequence analysis of compound-resistant mutants suggests that the viral 2C protein is targeted by most of these compounds. These compounds demonstrated antiviral activity against a panel of the most commonly encountered enteroviruses and thus represent potential leads for the development of broad-spectrum anti-enteroviral drugs.

Assembly of VP26 in herpes simplex virus-1 capsid implicated by 3-D structure of recombinant capsid

1995 ◽  
Vol 53 ◽  
pp. 840-841
Author(s):  
Z. Hong Zhou ◽  
Jing He ◽  
Joanita Jakana ◽  
J. D. Tatman ◽  
Frazer J. Rixon ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
3D Structure ◽  
Structure Study ◽  
Herpes Simplex Virus 1 ◽  
Shell Proteins ◽  
Life Threatening ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus-1 (HSV-1) is a ubiquitous virus which is implicated in diseases ranging from self-curing cold sores to life-threatening infections. The 2500 Å diameter herpes virion is composed of a glycoprotein spike containing, lipid envelope, enclosing a protein layer (the tegument) in which is embedded the capsid (which contains the dsDNA genome). The B-, and A- and C-capsids, representing different morphogenetic stages in HSV-1 infected cells, are composed of 7, and 5 structural proteins respectively. The three capsid types are organized in similar T=16 icosahedral shells with 12 pentons, 150 hexons, and 320 connecting triplexes. Our previous 3D structure study at 26 Å revealed domain features of all these structural components and suggested probable locations for the outer shell proteins, VP5, VP26, VP19c and VP23. VP5 makes up most of both pentons and hexons. VP26 appeared to bind to the VP5 subunit in hexon but not to that in penton.

Resveratrol: A new potential therapeutic agent for melanoma?

2019 ◽  
Vol 26 ◽  
Author(s):  
Mohamad Hossein Pourhanifeh ◽  
Kazem Abbaszadeh-Goudarzi ◽  
Mohammad Goodarzi ◽  
Sara G.M. Piccirillo ◽  
Alimohammad Shafiee ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Therapeutic Agent ◽  
Current Knowledge ◽  
Treatment Resistance ◽  
Anti Cancer ◽  
Apoptosis Inducer ◽  
Life Threatening ◽  
First Time

: Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard anti-melanomatreatments such as chemotherapy, and 5-year survival rate of cases with melanoma who have metastatic form of disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approachesthat couldenhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy. : Herein, for first time, we summarize current knowledge of anti-cancerous activities of resveratrol in melanoma.

scholarly journals Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity

2021 ◽  
Vol 22 (13) ◽  
pp. 7205
Author(s):  
Matheus V. C. Grahl ◽  
Augusto F. Uberti ◽  
Valquiria Broll ◽  
Paula Bacaicoa-Caruso ◽  
Evelin F. Meirelles ◽  
...  
Keyword(s):  
Proteus Mirabilis ◽  
Stone Formation ◽  
Cell Types ◽  
Bioinformatic Analysis ◽  
Urinary Stone ◽  
Enzymatic Properties ◽  
Hek293 Cells ◽  
Urinary Stones ◽  
Isolated Cells ◽  
Tnf Α

Infection by Proteus mirabilis causes urinary stones and catheter incrustation due to ammonia formed by urease (PMU), one of its virulence factors. Non-enzymatic properties, such as pro-inflammatory and neurotoxic activities, were previously reported for distinct ureases, including that of the gastric pathogen Helicobacter pylori. Here, PMU was assayed on isolated cells to evaluate its non-enzymatic properties. Purified PMU (nanomolar range) was tested in human (platelets, HEK293 and SH-SY5Y) cells, and in murine microglia (BV-2). PMU promoted platelet aggregation. It did not affect cellular viability and no ammonia was detected in the cultures’ supernatants. PMU-treated HEK293 cells acquired a pro-inflammatory phenotype, producing reactive oxygen species (ROS) and cytokines IL-1β and TNF-α. SH-SY5Y cells stimulated with PMU showed high levels of intracellular Ca2+ and ROS production, but unlike BV-2 cells, SH-SY5Y did not synthesize TNF-α and IL-1β. Texas Red-labeled PMU was found in the cytoplasm and in the nucleus of all cell types. Bioinformatic analysis revealed two bipartite nuclear localization sequences in PMU. We have shown that PMU, besides urinary stone formation, can potentially contribute in other ways to pathogenesis. Our data suggest that PMU triggers pro-inflammatory effects and may affect cells beyond the renal system, indicating a possible role in extra-urinary diseases.

scholarly journals EXPRESS: Pulmonary Hypertension Associated With Neurofibromatosis Type 2

2021 ◽  
pp. 204589402110295
Author(s):  
Hirohisa Taniguchi ◽  
Tomoya Takashima ◽  
Ly Tu ◽  
Raphaël Thuillet ◽  
Asuka Furukawa ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Neurofibromatosis Type ◽  
Pulmonary Vascular Remodeling ◽  
Life Threatening ◽  
History Of ◽  
Pulmonary Arterial ◽  
First Time

Although precapillary pulmonary hypertension (PH) is a rare but severe complication of patients with neurofibromatosis type 1 (NF1), its association with NF2 remains unknown. Herein, we report a case of a 44-year-old woman who was initially diagnosed with idiopathic pulmonary arterial hypertension (IPAH) and treated with PAH-specific combination therapy. However, a careful assessment for a relevant family history of the disease and genetic testing reveal that this patient had a mutation in the NF2 gene. Using immunofluorescence and Western blotting, we demonstrated a decrease in endothelial NF2 protein in lungs from IPAH patients compared to control lungs, suggesting a potential role of NF2 in PAH development. To our knowledge, this is the first time that precapillary PH has been described in a patient with NF2. The altered endothelial NF2 expression pattern in PAH lungs should stimulate work to better understand how NF2 is contributing to the pulmonary vascular remodeling associated to these severe life-threatening conditions.

scholarly journals Retention of adenovirus E19 glycoprotein in the endoplasmic reticulum is essential to its ability to block antigen presentation.

1991 ◽  
Vol 174 (6) ◽  
pp. 1629-1637 ◽  
Author(s):  
J H Cox ◽  
J R Bennink ◽  
J W Yewdell
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Antigen Presentation ◽  
Viral Proteins ◽  
Genetically Engineered ◽  
Class I ◽  
Wild Type ◽  
Histocompatibility Complex ◽  
Infected Cells ◽  
Lumenal Domain

The E3/19K glycoprotein of adenovirus functions to diminish recognition of adenovirus-infected cells by major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTLs) by binding intracellular class I molecules and preventing them from reaching the plasma membrane. In the present study we have characterized the nature of the interaction between E3/19K and the H-2Kd (Kd) molecule. An E3/19K molecule genetically engineered to terminate six residues from its normal COOH terminus (delta E19), was found to associate with Kd in a manner indistinguishable from wild-type E3/19K. Unlike E3/19K, however, delta E19 was transported through the Golgi complex to the plasma membrane, where it could be detected biochemically and immunocytochemically using a monoclonal antibody specific for the lumenal domain of E3/19K. Importantly, delta E19 also differed from E3/19K in being unable to prevent the presentation of Kd-restricted viral proteins to CTLs. This is unlikely to be due to delta E19 having a lower avidity for Kd than E3/19K, since delta E19 was able to compete with E3/19K for Kd binding, both physically, and functionally in nullifying the E3/19K blockade of antigen presentation. These findings indicate that the ability of E3/19K to block antigen presentation is due solely to its ability to retain newly synthesized class I molecules in the endoplasmic reticulum.

Cancer: A Life Threatening Peril Becoming Lifestyle Disease

2021 ◽  
pp. 03
Author(s):  
Sara Hayee ◽  
Amna Rehman
Keyword(s):  
Cancer Patients ◽  
Urban Areas ◽  
Past History ◽  
The World ◽  
Cause Of Deaths ◽  
Life Threatening ◽  
Abnormal Cells ◽  
Lifestyle Disease ◽  
First Time ◽  
Day By Day

Caner a dreadful disease is actually one large group of diseases which dates back to times of “Hippocrates”, The Father of Medicine, (460-370BC) who used this name for the first time to talk about non-ulcer and ulcer forming tumors. Theevidence of its presence from the very past history comes from fossilized “Egyptian Mummies” having tumors on bones. Then Galen (130-200 AD) used the term “Oncos” to explain tumors. So it's a disease involving growth of abnormal cells, their proliferation and metastasizing the other tissues and organs. Now we know that biology has a branch namedOncology to deal with the scientific study of cancer and oncogenes. It took centuries to get knowledge and use modern technologies against this malady. Now we know cancer is a group disease which has hundreds of types. 19th Century saw much advancement towards its cure. Along with surgery, radiotherapy and chemotherapy were the main methods to cure cancer patients. Day by day, scientists are looking for new methods to control and cure of this curse. Hundreds of natural medicinal compounds are being tested to use clinically for its cure in order to replace the radiotherapy andchemotherapy and lower their side effects. But humanity is still fighting against this disease as the numbers of cases throughout the world are increasing day by day. If we look on the reports p r e s e n t e d b y W H O ( W o r l d H e a l t hOrganization), Cancer is the second leading cause of deaths globally which means one person in every six deaths, dies due to cancer. In 2018, the most common types of cancers reported in men were of liver, prostate, stomach, lung andcolorectal. Whereas in females the most common forms were breast, thyroid, cervical and colorectal. Cancer has become a global disasterfamily of the patient. It imparts physical, emotional and financial crisis. Unfortunately, the condition is bitterer in under developing countries. Cancer has become a lifestyle disease these days. We are living in the world withsuperficial comfort but we are breathing with urbanizations, ozone depletion, exposure to microwave and ultraviolet radiations, hazardous chemicals etc. Moreover, It is becoming a lifestyle disease due to lack of exercise, Obesity, consumptions of drugs, tobacco and alcohols. The cases of cancers are reported more in urban areas than in rural areasmore likely due to above mentioned factors. The ratio of cancer patients is expected to raise up-to 27.5 million by 2040 globally. So the battle is never ending, Humans need to figure out the factors and cutting these from their lives in orderto live a healthy life which is a blessing indeed. which is not only crunching the cancer patient but it also has damaging effects on the whole

scholarly journals Exosomes derived from HTLV-1 infected cells contain viral proteins and mRNA

Retrovirology ◽  
2015 ◽  
Vol 12 (S1) ◽  
Author(s):  
Elizabeth Jaworski ◽  
Rachel Van Duyne ◽  
Sergey Iordanskiy ◽  
Philippe Afonso ◽  
Gavin Sampey ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Infected Cells
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