Veterinary Immunology and Immunopathology 159 (2014) 171–179 Contents lists available at ScienceDirect Veterinary Immunology and Immunopathology j ourna l h omepa ge: www.elsevier.com/locate/vetimm FIV in cats – a useful model of HIV in people? Dorothee Bienzle ∗ Department of Pathobiology, University of Guelph, Guelph, ON, Canada a r t i c l e i n f o Keywords: AIDS CXCR4 Feline Immunodeficiency Lentivirus Retrovirus a b s t r a c t The feline immunodeficiency virus (FIV) shares genomic organization, receptor usage, lym- phocyte tropism, and induction of immunodeficiency and increased susceptibility to cancer with the human immunodeficiency virus (HIV). Global distribution, marked heterogeneity and variable host adaptation are also properties of both viruses. These features render the FIV-cat model suitable to explore many aspects of lentivirus-host interaction and adap- tation, and to explore treatment and prevention of infection. Examples of fundamental discoveries that have emerged from study in the FIV-cat model concern two-receptor entrance strategies that target memory T-lymphocytes, host factors that restrict retro- viral infection, viral strategies for replication in non-dividing cells, and identification of correlates of immunity to the virus. This article provides a brief overview of strengths and limitations of the FIV-cat model for comparative biology and medicine. © 2014 Elsevier B.V. All rights reserved. 1. Primate lentiviruses Vertebrates are host to numerous retroviruses and retrovirus-derived genomic elements. Most replication- competent retroviruses in mammals have small RNA genomes coding for structural proteins and enzymes essential for replication. Lentiviruses are a group of retro- viruses that infect non-dividing cells and induce gradually progressive disease. They have the standard retroviral genome plus accessory genes that allow for more com- plex interactions with host cells. Among the lentiviruses only few have lymphocyte tropism and propensity to induce immunodeficiency. The primate and feline immu- nodeficiency viruses (HIV, SIV and FIV) are unique in that regard, and distinct from the largely macrophage-tropic lentiviruses of ungulates. The discovery of HIV as the cause of acquired immunodeficiency and a global epidemic with high mortality and morbidity has spurred intense research ∗ Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada. Tel.: +1 519 824 4120x54351; fax: +1 519 824 5930. E-mail address: dbienzle@uoguelph.ca into host-lentivirus interactions in multiple mammalian species. Evidence is now indisputable that several indepen- dent transmissions of SIV from monkeys to humans gave rise to the HIV epidemic (Sharp and Hahn, 2011). SIV is estimated to have been in different species of Old World monkeys for more than 30,000 years. In its native host, SIV causes little apparent disease despite high viral burden, suggesting a high degree of host adaptation. Chimpanzees have more recently acquired a recombinant SIV (SIVcpz) originating from two other species of monkey, and in chim- panzees in the wild SIV infection was associated with an increased risk of death (Rudicell et al., 2010). HIV-1 in humans first arose in west central Africa from cross-species transmission of SIVcpz to humans, presumably through blood exchange. Subgroups of HIV-1 are more similar to their SIVcpz counterpart than to each other (Hahn et al., 2000), indicating there were likely multiple independent transmissions. More rapid generation of genetic diversity in lentiviral than mammalian genomic DNA has allowed estimates of transmission dates, and shown that there is increased mortality after transmission to new hosts. Hence, estimates of viral evolution suggest initial transmissions of SIVcpz to humans occurred little more than 100 years http://dx.doi.org/10.1016/j.vetimm.2014.02.014 0165-2427/© 2014 Elsevier B.V. All rights reserved.