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      Felis Catus Gammaherpesvirus 1 DNAemia in Whole Blood from Therapeutically Immunosuppressed or Retrovirus-Infected Cats

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          Abstract

          Gammaherpesviruses are major co-pathogens of human immunodeficiency virus (HIV) infection, making the interactions between feline immunodeficiency virus (FIV) and Felis catus gammaherpesvirus 1 (FcaGHV1) pertinent to both human and veterinary medical research. FIV-infected cats are at increased risk of FcaGHV1 DNAemia and consistently harbor higher FcaGHV1 loads than FIV-uninfected cats. Whether immune deficiencies unrelated to FIV are associated with similar risks is unknown. Using whole blood FcaGHV1 qPCR, we found no difference in the frequency of DNAemia or DNA load in therapeutically immunosuppressed (P1, n = 18) or feline leukemia virus (FeLV)-infected (P2, n = 57) patients compared with age- and sex-matched controls (C1, n = 58; C2, n = 57). In contrast, FIV/FeLV-co-infected cats (P3, n = 5) were at increased risk of FcaGHV1 DNAemia compared to retrovirus uninfected controls (C3, n = 39; p = 0.0068), and had a higher median FcaGHV1 DNA load, although the latter was not significant. FIV/FeLV-co-infected cats (P3) had a similar frequency of FcaGHV1 DNAemia reported compared to FIV-infected controls (C4). In conclusion, we found no evidence that cats with therapeutic immunosuppression or FeLV infection were at greater risk of FcaGHV1 DNAemia or had higher FcaGHV1 DNA load in whole blood. The risk of DNAemia in FIV/FeLV-co-infected cats was similar to that documented previously in cats infected with FIV alone.

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          Global burden of deaths from Epstein-Barr virus attributable malignancies 1990-2010

          Background Epstein-Barr virus (EBV) is an oncogenic virus implicated in the pathogenesis of a number of human malignancies of both lymphoid and epithelial origin. Thus, a comprehensive and up-to-date analysis focused on the global burden of EBV-attributable malignancies is of significant interest. Methods Based on published studies, we estimated the proportion of Burkitt’s lymphoma (BL), Hodgkin’s lymphoma (HL), nasopharyngeal carcinoma NPC), gastric carcinoma (GC) and post-transplant lymphoproliferative disease (PTLD) attributable to EBV, taking into consideration age, sex and geographical variations. This proportion was then imputed into the Global Burden of Disease 2010 dataset to determine the global burden of each EBV-attributable malignancy in males and females in 20 different age groups and 21 world regions from 1990 to 2010. Results The analysis showed that the combined global burden of deaths in 2010 from all EBV-attributable malignancies was 142,979, representing 1.8% of all cancer deaths. This burden has increased by 14.6% over a period of 20 years. All 5 EBV-attributable malignancies were more common in males in all geographical regions (ratio of 2.6:1). Gastric cancer and NPC accounted for 92% of all EBV-attributable cancer deaths. Almost 50% of EBV-attributed malignancies occurred in East Asia. This region also had the highest age-standardized death rates for both NPC and GC. Conclusions Approximately 143,000 deaths in 2010 were attributed to EBV-associated malignancies. This figure is likely to be an underestimate since some of the less prevalent EBV-associated malignancies have not been included. Moreover, the global increase in population and life-expectancy will further increase the overall burden of EBV-associated cancer deaths. Development of a suitable vaccine could have a substantial impact on reducing this burden. Electronic supplementary material The online version of this article (doi:10.1186/1750-9378-9-38) contains supplementary material, which is available to authorized users.
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            Feline immunodeficiency virus (FIV) as a model for study of lentivirus infections: parallels with HIV.

            FIV is a significant pathogen in the cat and is, in addition, the smallest available natural model for the study of lentivirus infections. Although divergent at the amino acid level, the cat lentivirus has an abundance of structural and pathophysiological commonalities with HIV and thus serves well as a model for development of intervention strategies relevant to infection in both cats and man. The following review highlights both the strengths and shortcomings of the FIV/cat model, particular as regards development of antiviral drugs.
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              Feline leukemia virus infection and diseases.

              Feline leukemia virus is a naturally occurring, contagiously transmitted and oncogenic immunosuppressive retrovirus of cats. The effects of FeLV are paradoxical, causing cytoproliferative and cytosuppressive disease (eg, lymphoma and myeloproliferative disorders vs immunodeficiency and myelosuppressive disorders). In the first few weeks after virus exposure, interactions between FeLV and hemolymphatic system cells determine whether the virus or the cat will dominate in the host/virus relationship--persistent viremia and progressive infection or self limiting, regressive infection will develop. The outcome of these early host/virus interactions is revealed in the diagnostic assays for FeLV antigenemia and viremia. The latter, in turn, predict the outcome of FeLV infection in cats. Known host resistance factors include age and immune system functional status. Known virus virulence factors are magnitude of exposure and virus genotype. Molecular analysis of FeLV strains indicated that natural virus isolates exist as mixtures of closely related virus genotypes and that minor genetic variations among FeLV strains can impart major differences in pathogenicity. The genetic coding regions responsible for cell targeting and specific disease inducing capacity (eg, thymic lymphoma, acute immunosuppression, or aplastic anemia) have been mapped to the virus surface glycoprotein and/or long terminal repeat regions for several FeLV strains. Infection by specific FeLV strains leads to either malignant transformation or cytopathic deletion of specific lymphocyte and hemopoietic cell population, changes that prefigure the onset of clinical illness. Another notable feature of the biology of FeLV is that many cats are able to effectively contain and terminate viral replication, an important example of host immunologic control of a retrovirus infection and a process that can be selectively enhanced by vaccination. Thus, FeLV infection serves as a natural model of the multifaceted pathogenesis of retroviruses and as a paradigm for immunoprophylaxis against an immunosuppressive leukemogenic retrovirus.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Vet Sci
                Vet Sci
                vetsci
                Veterinary Sciences
                MDPI
                2306-7381
                14 March 2017
                March 2017
                : 4
                : 1
                : 16
                Affiliations
                [1 ]Faculty of Science, Sydney School of Veterinary Science, The University of Sydney, Sydney, NSW 2006, Australia; amcl8135@ 123456uni.sydney.edu.au (A.J.M.); vanessa.barrs@ 123456sydney.edu.au (V.R.B.); mark.westman@ 123456sydney.edu.au (M.E.W.)
                [2 ]Faculty of Science, School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia; bethany@ 123456cafallstats.com.au
                Author notes
                [* ]Correspondence: julia.beatty@ 123456sydney.edu.au ; Tel.: +61-2-9351-3437
                Article
                vetsci-04-00016
                10.3390/vetsci4010016
                5606616
                2c381afb-0deb-4465-b641-576fe764f134
                © 2017 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
                : 17 January 2017
                : 10 March 2017
                Categories
                Article

                gammaherpesvirus,retrovirus,co-infection,immunodeficiency,immunosuppression,lymphoma,comparative medicine

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