Genetic susceptibility, HIV infection, and the kidney
ABSTRACT In recent years, the sequencing of mammalian and microbial genomes has provided the opportunity to study how genetic variation in the host and pathogen influence the course of infectious disease. In the case of HIV-1 infection, such studies have led to identification of key viral proteins that determine pathogenicity, immune evasion, or drug resistance. In addition, candidate gene association studies have uncovered a large number of host genetic variants that influence the outcome of infection and some organ-specific complications. HIV-associated nephropathy (HIVAN) is a pathologically distinct complication of HIV infection. Interindividual variability in incidence, skewed ethnic distribution, and familial aggregation of HIVAN with other forms of ESRD have suggested genetic susceptibility as a major contributing factor. This article reviews the host genetic factors that influence the course of HIV-1 infection and discusses murine models that have increased the understanding of HIVAN pathogenesis and demonstrated the role of genetic background on determination of disease.
Article: HIV and the kidney.[Show abstract] [Hide abstract]
ABSTRACT: Kidney disease is an important complication of HIV infection. Antiretroviral therapy has dramatically improved the life expectancy of HIV-infected patients with end-stage renal disease. Renal replacement therapy, including kidney transplantation, should be offered to HIV-positive patients.British journal of hospital medicine (London, England: 2005) 04/2008; 69(3):137-40. · 0.37 Impact Factor
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ABSTRACT: After half a century of success in combating infectious diseases with vaccination and antibiotics, emerging and reemerging epidemics present a new threat to human health. Meanwhile, the rapid pace of viral and microbial genomics research, largely based on the success of genomics technologies, offers new data-generating platforms and a revolutionary knowledge base for better understanding the diseases and the associated pathogens. Systematic molecular biology studies using genomics information and technologies have helped to elucidate mechanisms of virulence and pathogenicity, whereas genomics-based medical genetic studies have been used to better understand pathogen susceptibility. This progress may lead to the development of effective and safe vaccines in the future. Here we highlight the ongoing historical transition in the field of infectious disease research and clinical practice in the new era of genomics.Annual Review of Genomics and Human Genetics 10/2008; 9:21-48. DOI:10.1146/annurev.genom.9.081307.164428 · 9.13 Impact Factor
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ABSTRACT: Full length, eukaryotic proteins generally consist of several autonomously folding and functioning domains. Many of these domains are known to function by binding and/or modifying other partner proteins based on the recognition of a short, linear amino sequence contained within the target protein. This article reviews the many bioinformatic tools and resources which discover, define and catalogue the various, known protein domains as well as assist users by identifying domain signatures within proteins of interest. We also review the smaller subset of bioinformatic tools which catalogue and help identify the short linear motifs used for domain targeting. It has been suggested that these short, functional, peptide-sequence motifs are normally found in unstructured regions of the target. The role of protein structure in the activity of one representative of these short, functional motifs is explored through an examination of known structures deposited in the Protein Data Bank.Frontiers in Bioscience 02/2009; 14:1143-51. DOI:10.2741/3299 · 4.25 Impact Factor