Viruses and kidney disease: beyond HIV

Abstract

Human immunodeficiency virus (HIV)-infected patients may acquire new viral co-infections; they also may experience the reactivation or worsening of existing viral infections, including active, smoldering, or latent infections. HIV-infected patients may be predisposed to these viral infections owing to immunodeficiency or risk factors common to HIV and other viruses. A number of these affect the kidney, either by direct infection or by deposition of immune complexes. In this review we discuss the renal manifestations and treatment of hepatitis C virus, BK virus, adenovirus, cytomegalovirus, and parvovirus B19 in patients with HIV disease. We also discuss an approach to the identification of new viral renal pathogens, using a viral gene chip to identify viral DNA or RNA.

Figure 1. Histologic appearance of virally-infected kidney cells. [COLOR]

Polyoma infection: Renal allograft biopsy showing tubulointerstitial damage. Some tubular epithelial cells exhibit finely granular and markedly enlarged nuclei with a ground glass appearance (arrowhead) which is typically seen in polyoma virus nephropathy. A mononuclear cell infiltrate is present (periodic acid–Schiff stain magnification 200x). Immunohistochemical staining for SV40 T antigen demonstrates numerous nuclei of tubular epithelial cells in 1 tubular profile with reaction product (immunoperoxidase; magnification 200x) (Reprinted with permission (30)) Cytomegalovirus infection: Kidney tissue showing characteristic large cells with basophilic intranuclear inclusions which has the appearance of an “owl’s eye”. There are also prominent red cytoplasmic inclusions. (Hematoxylin-eosin stain; magnification 600x). Adenovirus infection: Kidney tissue from an immunosuppressed patient shows necrosis of tubular epithelial cells. Infected tubular cells have enlarged basophilic nuclei with smudged appearance which is characteristic of adenovirus (Hematoxylin-eosin stain).

Figure 2. Identifying novel or unexpected viruses using a viral gene chip. [COLOR]

The starting material is typically RNA obtained from cells, tumor tissue, blood, urine or other body fluids. After first DNA strand synthesis with reverse transcriptase, the first and second DNA strands are amplified using a random PCR protocol and standard primers A and B as described (87). The cDNA is used in a subsequent 40 cycle PCR using a specific primer designed to amplify the template. The same primer is used in an additional 20 cycles of PCR that incorporates random primed oligomers in the presence of aminoallyl-dUTP thus allowing labeling with the fluorescent molecule Cy3. Once purified, the Cy3-labelled DNA is pre-annealed with human cot-1 DNA and Agilent blocking and hybridization buffers before hybridizing onto the Agilent microarray bearing the sequences from viral open reading frames. A standard custom microarray Agilent protocol is employed to wash the microarray before scanning.