A5080281045- Viral Infections and Vectors
- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- Phagocytosis and Immune Regulation
- interferon and immune responses
- Drug Transport and Resistance Mechanisms
- HIV Research and Treatment
- Complement system in diseases
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- RNA regulation and disease
- RNA Research and Splicing
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- Antibiotics Pharmacokinetics and Efficacy
- Asthma and respiratory diseases
- Immune Cell Function and Interaction
- Inhalation and Respiratory Drug Delivery
Leiden University Medical Center
2019-2025
Centre for Human Drug Research
2019
The coronavirus papain-like protease (PLpro) is crucial for viral replicase polyprotein processing. Additionally, PLpro can subvert host defense mechanisms by its deubiquitinating (DUB) and deISGylating activities. To elucidate the role of these activities during SARS-CoV-2 infection, we introduced mutations that disrupt binding to ubiquitin or ISG15. We identified several strongly reduced DUB activity PLpro, without affecting In contrast, abrogated also hampered processing when into virus...
Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and in particular the interferon response form important first line of defense against these viruses. Given their genetic flexibility, have therefore developed multiple strategies to evade order optimize replication capacity. Already molecular mechanisms evasion by +ssRNA been identified. However, research addressing effect host on...
Usutu virus (USUV) is an emerging flavivirus that can infect birds and mammals. In humans, in severe cases, it may cause neuroinvasive disease. The innate immune system, particular the interferon response, functions as important first line of defense against invading pathogens such USUV. Many, if not all, viruses have developed mechanisms to suppress and/or evade response order facilitate their replication. ability USUV antagonize has so far remained largely unexplored. Using dual-luciferase...
Concentrations of drugs acting in the lungs are difficult to measure, resulting relatively unknown local pharmacokinetics. The aim this study is assess potential exhaled breath condensate (EBC) as a matrix for pharmacokinetic analysis inhaled and intravenous medication. A 4‐way crossover was conducted 12 volunteers with tobramycin salbutamol intravenously via inhalation. EBC plasma samples were collected postdose analysed drug concentrations. Sample dilution, calculated using urea...
Abstract Vault RNAs (vtRNAs) are a family of four small non-coding (ncRNAs) that ubiquitously expressed in many eukaryotes and regulate multiple cellular pathways. Their expression is increased upon infection with various DNA RNA viruses. This suggests they either co-opted by the virus to aid replication or function as an antiviral restriction factor. However, their precise molecular remains unclear. Here, we show picornaviruses, alphaviruses, beta-coronaviruses broadly enhances vtRNA...
Factor H is a pivotal complement regulatory protein that preferentially produced by the liver and circulates in high concentrations serum. There has been an increasing interest extrahepatic production of factors, including cells immune system, since this contributes to non-canonical functions local activation regulation. Here we investigated regulation factor its splice variant H-like 1 (FHL-1) human myeloid cells. As validation, confirmed predominant presence intact serum, despite strong...