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      Renal Alterations in Feline Immunodeficiency Virus (FIV)-Infected Cats: A Natural Model of Lentivirus-Induced Renal Disease Changes

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          Abstract

          Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

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          An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction.

          W. Reid, M SADOWSKA, F Denaro … (2001)
          We report, to our knowledge, the first HIV type 1 (HIV-1) transgenic (Tg) rat. Expression of the transgene, consisting of an HIV-1 provirus with a functional deletion of gag and pol, is regulated by the viral long terminal repeat. Spliced and unspliced viral transcripts were expressed in lymph nodes, thymus, liver, kidney, and spleen, suggesting that Tat and Rev are functional. Viral proteins were identified in spleen tissue sections by immunohistochemistry and gp120 was present in splenic macrophages, T and B cells, and in serum. Clinical signs included wasting, mild to severe skin lesions, opaque cataracts, neurological signs, and respiratory difficulty. Histopathology included a selective loss of splenocytes within the periarterial lymphoid sheath, increased apoptosis of endothelial cells and splenocytes, follicular hyperplasia of the spleen, lymphocyte depletion of mesenteric lymph nodes, interstitial pneumonia, psoriatic skin lesions, and neurological, cardiac, and renal pathologies. Immunologically, delayed-type hypersensitivity response to keyhole limpet hemocyanin was diminished. By contrast, Ab titers and proliferative response to recall antigen (keyhole limpet hemocyanin) were normal. The HIV-1 Tg rat thus has many similarities to humans infected with HIV-1 in expression of viral genes, immune-response alterations, and pathologies resulting from infection. The HIV-1 Tg rat may provide a valuable model for some of the pathogenic manifestations of chronic HIV-1 diseases and could be useful in testing therapeutic regimens targeted to stages of viral replication subsequent to proviral integration.
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            Feline immunodeficiency. ABCD guidelines on prevention and management

            Margaret Hosie, Diane D. Addie, Sándor Belák … (2009)
            Overview Feline immunodeficiency virus (FIV) is a retrovirus closely related to human immunodeficiency virus. Most felids are susceptible to FIV, but humans are not. Feline immunodeficiency virus is endemic in domestic cat populations worldwide. The virus loses infectivity quickly outside the host and is susceptible to all disinfectants. Infection Feline immunodeficiency virus is transmitted via bites. The risk of transmission is low in households with socially well-adapted cats. Transmission from mother to kittens may occur, especially if the queen is undergoing an acute infection. Cats with FIV are persistently infected in spite of their ability to mount antibody and cell-mediated immune responses. Disease signs Infected cats generally remain free of clinical signs for several years, and some cats never develop disease, depending on the infecting isolate. Most clinical signs are the consequence of immunodeficiency and secondary infection. Typical manifestations are chronic gingivostomatitis, chronic rhinitis, lymphadenopathy, weight loss and immune-mediated glomerulonephritis. Diagnosis Positive in-practice ELISA results obtained in a low-prevalence or low-risk population should always be confirmed by a laboratory. Western blot is the ‘gold standard’ laboratory test for FIV serology. PCR-based assays vary in performance. Disease management Cats should never be euthanased solely on the basis of an FIV-positive test result. Cats infected with FIV may live as long as uninfected cats, with appropriate management. Asymptomatic FIV-infected cats should be neutered to avoid fighting and virus transmission. Infected cats should receive regular veterinary health checks. They can be housed in the same ward as other patients, but should be kept in individual cages. Vaccination recommendations At present, there is no FIV vaccine commercially available in Europe. Potential benefits and risks of vaccinating FIV-infected cats should be assessed on an individual cat basis. Needles and surgical instruments used on FIV-positive cats may transmit the virus to other cats, so strict hygiene is essential.
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              Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy.

              Mahesh Mansukhani, Pauline M. Ross, D Marras … (2002)
              HIV-associated nephropathy is a clinicopathologic entity that includes proteinuria, focal segmental glomerulosclerosis often of the collapsing variant, and microcystic tubulointerstitial disease. Increasing evidence supports a role for HIV-1 infection of renal epithelium in the pathogenesis of HIV-associated nephropathy. Using in situ hybridization, we previously demonstrated HIV-1 gag and nef mRNA in renal epithelial cells of patients with HIV-associated nephropathy. Here, to investigate whether renal epithelial cells were productively infected by HIV-1, we examined renal tissue for the presence of HIV-1 DNA and mRNA by in situ hybridization and PCR, and we molecularly characterized the HIV-1 quasispecies in the renal compartment. Infected renal epithelial cells were removed by laser-capture microdissection from biopsies of two patients, DNA was extracted, and HIV-1 V3-loop or gp120-envelope sequences were amplified from individually dissected cells by nested PCR. Phylogenetic analysis of kidney-derived sequences as well as corresponding sequences from peripheral blood mononuclear cells of the same patients revealed evidence of tissue-specific viral evolution. In phylogenetic trees constructed from V3 and gp120 sequences, kidney-derived sequences formed tissue-specific subclusters within the radiation of blood mononuclear cell-derived viral sequences from both patients. These data, along with the detection of HIV-1-specific proviral DNA and mRNA in tubular epithelium cells, argue strongly for localized replication of HIV-1 in the kidney and the existence of a renal viral reservoir.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Viruses
                Journal ID (iso-abbrev): Viruses
                Journal ID (publisher-id): viruses
                Title: Viruses
                Publisher: MDPI
                ISSN (Electronic): 1999-4915
                Publication date (Electronic): 27 August 2012
                Publication date Collection: September 2012
                Volume: 4
                Issue: 9
                Pages: 1372-1389
                Affiliations
                [1 ] Department of Animal Pathology, Prophylaxis and Food Hygiene, Veterinary Faculty, University of Pisa, Viale delle Piagge 2, Pisa 56124, Italy; Email: apoli@ 123456vet.unipi.it
                [2 ] Clinic for Small Animal Medicine and Surgery, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, Ljubljana 1000, Slovenia; Email: Natasa.Tozon@ 123456vf.uni-lj.si
                [3 ] Department of Veterinary Clinic, Veterinary Faculty, University of Pisa, Via Livornese, San Piero a Grado, Pisa 56122, Italy; Email: guidi@ 123456vet.unipi.it
                [4 ] Department of Experimental Pathology, University of Pisa, Via S. Zeno, 35/39, Pisa 56127, Italy
                Author notes
                [* ] Author to whom correspondence should be addressed; Email: mauro.pistello@ 123456med.unipi.it ; Tel.: +39-050-221-3781; Fax: +39-050-221-3524.
                Article
                Publisher ID: viruses-04-01372
                DOI: 10.3390/v4091372
                PMC ID: 3499810
                PubMed ID: 23170163
                SO-VID: 676b4590-8506-4087-a6e8-820a5a8a6596
                Copyright © © 2012 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 18 July 2012
                Date revision received : 15 August 2012
                Date accepted : 16 August 2012
                Categories
                Subject: Article

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: kidney diseases,fiv,feline immunodeficiency virus,renal pathology,cat
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: kidney diseases, fiv, feline immunodeficiency virus, renal pathology, cat

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