Publications
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The Emerging Role of the Gut Virome in Health and Inflammatory Bowel Disease: Challenges, Covariates and a Viral Imbalance KU Leuven
Virome research is a rapidly growing area in the microbiome field that is increasingly associated with human diseases, such as inflammatory bowel disease (IBD). Although substantial progress has been made, major methodological challenges limit our understanding of the virota. In this review, we describe challenges that must be considered to accurately report the virome composition and the current knowledge on the virome in health and IBD. First, ...
Alzheimer's disease: Old problem, new views from transgenic and viral models KU Leuven
Alzheimer's dementia is developing ever more as a complex syndrome with various unknown genetic and epigenetic contributions. These are compounded on and exacerbating the underlying amyloid and tau pathology that remain the basis of the pathological definition of Alzheimer's disease. Here, we present a selection of aspects of recent bigenic and virus-based mouse strains, developed as pre-clinical models for Alzheimer's disease. We discuss newer ...
Human viral diseases: what is next for antiviral drug discovery? KU Leuven
For the treatment of human immunodeficiency virus (HIV) infections for which there are ample drugs available, the immediate future lies in a once-daily combination pill containing three or four active ingredients. This strategy may also be envisaged for the treatment of hepatitis C virus (HCV) infections as soon as we have at hand the appropriate direct-acting antiviral agents (DAAs) to be combined. A combination drug therapy is generally not ...
Decompensation in Advanced Nonalcoholic Fatty Liver Disease May Occur at Lower Hepatic Venous Pressure Gradient Levels Than in Patients With Viral Disease KU Leuven University of Antwerp
BACKGROUND & AIMS: Portal hypertension is the strongest predictor of hepatic decompensation and death in patients with cirrhosis. However, its discriminatory accuracy in patients with nonalcoholic fatty liver disease (NAFLD) has been challenged because hepatic vein catheterization may not reflect the real portal vein pressure as accurately as in patients with other etiologies. We aimed to evaluate the relationship between hepatic venous ...
Longitudinal follow-up and characterization of a robust rat model for Parkinson's disease based on overexpression of alpha-synuclein with adeno-associated viral vectors. Vrije Universiteit Brussel
Testing of new therapeutic strategies for Parkinson's disease (PD) is currently hampered by the lack of relevant and reproducible animal models. Here, we developed a robust rat model for PD by injection of adeno-associated viral vectors (rAAV2/7) encoding α-synuclein into the substantia nigra, resulting in reproducible nigrostriatal pathology and behavioral deficits in a 4-week time period. Progressive dopaminergic dysfunction was corroborated ...
JC viral loads in patients with Crohn's disease treated with immunosuppression: can we screen for elevated risk of progressive multifocal leukoencephalopathy? KU Leuven
BACKGROUND AND AIMS: Anti-alpha4 integrin therapy with natalizumab is efficacious in refractory Crohn's disease and in multiple sclerosis, but carries an estimated 1/1000 risk of progressive multifocal leukoencephalopathy (PML) caused by reactivation of latent JC virus infection. Although anti-alpha4 integrin therapies are likely to be introduced in the clinic, screening for the risk of PML has not been developed. METHODS: We prospectively ...
Development of an Alpha-synuclein Based Rat Model for Parkinson's Disease via Stereotactic Injection of a Recombinant Adeno-associated Viral Vector KU Leuven
In order to study the molecular pathways of Parkinson's disease (PD) and to develop novel therapeutic strategies, scientific investigators rely on animal models. The identification of PD-associated genes has led to the development of genetic PD models. Most transgenic α-SYN mouse models develop gradual α-SYN pathology but fail to display clear dopaminergic cell loss and dopamine-dependent behavioral deficits. This hurdle was overcome by direct ...
Development, characterization and validation of a rat model for Parkinson's disease based on viral vector mediated overexpression of A53T alpha-synuclein KU Leuven
Parkinsons disease (PD) is a progressive, age-related neurodegenerative movement disorder affecting about 12% of people above 60 years. Prominent neuropathological hallmarks of PD are the loss of the dopaminergic neurons in the substantia nigra and the presence of α-synuclein containing intracellular inclusions: Lewy bodies and Lewy neurietes. Alpha-synuclein, a protein of 140 amino acids localized in nerve terminals, is the major fibrillar ...
HIV-1 integrase variants retarget viral integration and are associated with disease progression in a chronic infection cohort KU Leuven
Distinct integration patterns of different retroviruses, including HIV-1, have puzzled virologists for over 20 years. A tetramer of the viral integrase (IN) assembles on the two viral cDNA ends, docks onto the target DNA (tDNA), and catalyzes viral genome insertion into the host chromatin. We identified the amino acids in HIV-1 IN that directly contact tDNA bases and affect local integration site sequence selection. These residues also determine ...