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Published on: August 9, 2013
Common Mechanisms of Viral Injury to the Kidney
1Departments of Inflammation & Immunity and Nephrology, Cleveland Clinic, and Case Western Reserve University School of Medicine, Cleveland, OH.
Abstract:
Viral infections in an immunocompetent host can cause both acute and chronic kidney diseases, either by direct damage to the infected kidney cells or as a consequence of systemic immune responses that impact the kidneys' function. Viruses have evolved mechanisms to hijack signaling pathways of the infected cell, including the mammalian target of rapamycin pathway to support viral replication, and to evade antiviral immune responses such as those mediated by miR-155 via microRNA mimetics expressed by the virus. At both the cellular and systemic levels, the host has also evolved mechanisms to counter the viral subversion strategies in the evolutionary battle for mutual survival. In the era of genomic medicine, understanding individual genetic variations that lead to differences in susceptibilities to infection and variabilities in immune responses may open new avenues for treatment, such as the recently described functions of apolipoprotein L1 risk alleles in HIV-associated nephropathy. In addition, state-of-the-art high-throughput sequencing methods have discovered new viruses as the cause for chronic diseases not previously attributed to an infection. The potential application of these methods to idiopathic kidney diseases may reveal similar occult infections by unknown viruses. Precision medicine objectives to optimize host-directed and pathogen-directed therapies for kidney diseases associated with infectious causes will only be achieved through detailed understanding of genetic susceptibility associated with immune responses and viral tropism.
Insights
Viral infections can cause kidney disease through direct cell damage or immune responses. Understanding genetic factors and using advanced sequencing may lead to new precision medicine treatments for these viral kidney diseases.
Area of Science:
- Nephrology
- Virology
- Immunology
- Genetics
Background:
- Viral infections are a significant cause of acute and chronic kidney diseases in immunocompetent individuals.
- Viruses employ sophisticated mechanisms to subvert host cell pathways (e.g., mammalian target of rapamycin) for replication and evade immune responses (e.g., microRNA mimetics).
- Host immune systems have evolved counter-mechanisms against viral evasion strategies, creating an ongoing evolutionary interplay.
Purpose of the Study:
- To explore the intricate relationship between viral infections and kidney diseases.
- To highlight the role of host genetic variations and immune responses in disease susceptibility and outcomes.
- To discuss the potential of advanced sequencing technologies and precision medicine in diagnosing and treating virus-associated kidney diseases.
Main Methods:
- Review of viral mechanisms in kidney pathogenesis, including cellular signaling pathway hijacking and immune evasion.
- Analysis of host genetic factors, such as apolipoprotein L1 risk alleles, in influencing susceptibility to viral nephropathies (e.g., HIV-associated nephropathy).
- Discussion of high-throughput sequencing technologies for identifying novel viral causes of kidney diseases, including idiopathic conditions.
Main Results:
- Viral infections can lead to kidney damage via direct cellular injury or indirect immune-mediated responses.
- Host genetic variations significantly impact susceptibility and immune response variability to viral kidney diseases.
- Advanced sequencing has identified previously unknown viruses linked to chronic kidney conditions, suggesting potential for discovering occult infections in idiopathic diseases.
Conclusions:
- Understanding the interplay between viral tropism, host genetics, and immune responses is crucial for developing effective therapies.
- Genomic medicine and precision approaches offer promising avenues for optimizing treatments for virus-associated kidney diseases.
- Further research utilizing advanced sequencing may uncover the viral etiology of currently unexplained kidney diseases, paving the way for targeted interventions.
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