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      Applications of the FIV Model to Study HIV Pathogenesis

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          Abstract

          Feline immunodeficiency virus (FIV) is a naturally-occurring retrovirus that infects domestic and non-domestic feline species, producing progressive immune depletion that results in an acquired immunodeficiency syndrome (AIDS). Much has been learned about FIV since it was first described in 1987, particularly in regard to its application as a model to study the closely related lentivirus, human immunodeficiency virus (HIV). In particular, FIV and HIV share remarkable structure and sequence organization, utilize parallel modes of receptor-mediated entry, and result in a similar spectrum of immunodeficiency-related diseases due to analogous modes of immune dysfunction. This review summarizes current knowledge of FIV infection kinetics and the mechanisms of immune dysfunction in relation to opportunistic disease, specifically in regard to studying HIV pathogenesis. Furthermore, we present data that highlight changes in the oral microbiota and oral immune system during FIV infection, and outline the potential for the feline model of oral AIDS manifestations to elucidate pathogenic mechanisms of HIV-induced oral disease. Finally, we discuss advances in molecular biology, vaccine development, neurologic dysfunction, and the ability to apply pharmacologic interventions and sophisticated imaging technologies to study experimental and naturally occurring FIV, which provide an excellent, but often overlooked, resource for advancing therapies and the management of HIV/AIDS.

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          Most cited references244

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          Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease.

          In addition to CD4, the human immunodeficiency virus (HIV) requires a coreceptor for entry into target cells. The chemokine receptors CXCR4 and CCR5, members of the G protein-coupled receptor superfamily, have been identified as the principal coreceptors for T cell line-tropic and macrophage-tropic HIV-1 isolates, respectively. The updated coreceptor repertoire includes numerous members, mostly chemokine receptors and related orphans. These discoveries provide a new framework for understanding critical features of the basic biology of HIV-1, including the selective tropism of individual viral variants for different CD4+ target cells and the membrane fusion mechanism governing virus entry. The coreceptors also provide molecular perspectives on central puzzles of HIV-1 disease, including the selective transmission of macrophage-tropic variants, the appearance of T cell line-tropic variants in many infected persons during progression to AIDS, and differing susceptibilities of individuals to infection and disease progression. Genetic findings have yielded major insights into the in vivo roles of individual coreceptors and their ligands; of particular importance is the discovery of an inactivating mutation in the CCR5 gene which, in homozygous form, confers strong resistance to HIV-1 infection. Beyond providing new perspectives on fundamental aspects of HIV-1 transmission and pathogenesis, the coreceptors suggest new avenues for developing novel therapeutic and preventative strategies to combat the AIDS epidemic.
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            Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the "red complex", a prototype polybacterial pathogenic consortium in periodontitis.

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              Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome.

              A highly T-lymphotropic virus was isolated from cats in a cattery in which all the animals were seronegative for feline leukemia virus. A number of cats in one pen had died and several had an immunodeficiency-like syndrome. Only 1 of 18 normal cats in the cattery showed serologic evidence of infection with this new virus, whereas 10 of 25 cats with signs of ill health were seropositive for the virus. Tentatively designated feline T-lymphotropic lentivirus, this new feline retrovirus appears to be antigenically distinct from human immunodeficiency virus. There is no evidence for cat-to-human transmission of the agent. Kittens experimentally infected by way of blood or plasma from naturally infected animals developed generalized lymphadenopathy several weeks later, became transiently febrile and leukopenic, and continued to show a generalized lymphadenopathy 5 months after infection.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                20 April 2018
                April 2018
                : 10
                : 4
                : 206
                Affiliations
                [1 ]Department of Veterinary Pathobiology, Oklahoma State University, Stillwater, OK 74078, USA
                [2 ]Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA; Zaid.Abdo@ 123456colostate.edu (Z.A.); Sue.Vandewoude@ 123456colostate.edu (S.V.)
                [3 ]Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65201, USA; EricssonA@ 123456missouri.edu
                [4 ]Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; jelder@ 123456scripps.edu
                Author notes
                [* ]Correspondence: craig.miller@ 123456okstate.edu ; Tel.: +1-405-744-2219
                Author information
                https://orcid.org/0000-0002-3638-5665
                Article
                viruses-10-00206
                10.3390/v10040206
                5923500
                29677122
                fae00d1f-9979-401a-b19b-2ec1c31e8c0b
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 March 2018
                : 17 April 2018
                Categories
                Review

                Microbiology & Virology
                feline immunodeficiency virus,fiv,human immunodeficiency virus,hiv,animal models,opportunistic disease,lentiviral pathogenesis,molecular biology

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