Genetic Susceptibility, HIV Infection, and the Kidney

Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Clinical Journal of the American Society of Nephrology (Impact Factor: 4.61). 08/2007; 2 Suppl 1(Supplement 1):S25-35. DOI: 10.2215/CJN.00320107
Source: PubMed


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.

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    • "In animal populations, susceptibility to virus infection and the modulation of disease progression display inter-individual variability [7–9]. The study of host factors that control disease susceptibility relies on the multi-approach analysis of individuals demonstrating a differential response to OsHV-1 exposure/infection. "
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    ABSTRACT: Background Massive mortality outbreaks affecting Pacific oyster (Crassostrea gigas) spat in various countries have been associated with the detection of a herpesvirus called ostreid herpesvirus type 1 (OsHV-1). However, few studies have been performed to understand and follow viral gene expression, as it has been done in vertebrate herpesviruses. In this work, experimental infection trials of C. gigas spat with OsHV-1 were conducted in order to test the susceptibility of several bi-parental oyster families to this virus and to analyze host-pathogen interactions using in vivo transcriptomic approaches. Results The divergent response of these oyster families in terms of mortality confirmed that susceptibility to OsHV-1 infection has a significant genetic component. Two families with contrasted survival rates were selected. A total of 39 viral genes and five host genes were monitored by real-time PCR. Initial results provided information on (i) the virus cycle of OsHV-1 based on the kinetics of viral DNA replication and transcription and (ii) host defense mechanisms against the virus. Conclusions In the two selected families, the detected amounts of viral DNA and RNA were significantly different. This result suggests that Pacific oysters are genetically diverse in terms of their susceptibility to OsHV-1 infection. This contrasted susceptibility was associated with dissimilar host gene expression profiles. Moreover, the present study showed a positive correlation between viral DNA amounts and the level of expression of selected oyster genes.
    BMC Genomics 07/2014; 15(1):580. DOI:10.1186/1471-2164-15-580 · 3.99 Impact Factor
    • "The most common kidney biopsy finding in AIDS has been found to be FSGS-collapsing variant.[1] CG is characterized by black racial predominance, massive proteinuria, relatively rapidly progressive renal insufficiency, and distinctive pathologic findings.[9] CG should be categorized as a separate disease entity because as compared with other variants of FSGS, collapsing FSGS often has global lesions involving >50% of the glomeruli with the highest level of injury to the glomeruli, tubules, and interstitium. "
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    ABSTRACT: Human immunodeficiency virus (HIV) involves glomerular, tubulointerstitial, and vascular compartments of the kidney. The most common glomerular lesion is HIV-associated focal segmental glomerulosclerosis (FSGS) and related mesangiopathies collectively termed HIV-associated nephropathy (HIVAN). A variety of immune-complex mediated glomerular diseases such as membranoproliferative glomerulonephritis (MPGN), IgA nephropathy, and lupus-like glomerulonephritis also occur. HIVAN is restricted to patients presenting with proteinuria and progressive reduction of renal function and with distinctive but not pathognomonic pathology (FSGS often coexisting with glomerular collapse and tubular microcystic dilatations). The worldwide incidence of collapsing glomerulopathy (CG) in HIV-positive patients is high in Americans. But in India and other Asian countries, other forms of kidney diseases are more commonly seen. We report the first case of CG in the state of Jammu and Kashmir which also happens to be a very low incidence belt for HIV.
    Indian Journal of Nephrology 10/2010; 20(4):211-3. DOI:10.4103/0971-4065.73451
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    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. · 0.38 Impact Factor
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