Our animal model of HIV infection employs EcoHIV, chimeric HIV clones in which the gp120 coding region is replaced by the coding region of the ecotropic murine leukemia virus (MLV) envelope, switching the viral tropism from human to rodent

1292 INTRODUCTION Since the recognition of acquired immune deficiency syndrome (AIDS), animal models have been developed to study various aspects of human immunodeficiency virus (HIV) infection, pathogenesis and control. The most common route of HIV transmission, sexual transmission (UNAIDS, 2012), has been investigated by simian immunodeficiency virus (SIV) infection of macaques and HIV infection of humanized mice. For infection, virus stock is applied to the female reproductive tract (FRT) or rectum, often after a course of progestin (Cranage et al., 2008; Denton et al., 2008; Denton et al., 2011; Miller et al., 2005; Sun et al., 2007). These animal models have shown the ability of some antiretrovirals in topical application or injection to prevent or reduce vaginal or rectal virus infection (Cranage et al., 2008; Denton et al., 2008; Denton et al., 2011; Sun et al., 2007). Physiological factors that can influence viral sexual transmission that are absent from these formats are semen as the inoculum, female hormonal cycle changes in susceptibility to infection, and the responses of the FRT to copulation. Semen from HIV-infected men contains cell-free virus and infected cells, and each can mediate infection (Quayle et al., 1997). Cytokines in semen can activate cells of the FRT and the levels of cytokines are higher during acute infection, when HIV sexual transmission is most efficient (Kafka et al., 2012; Lisco et al., 2012; Wawer et al., 2005). Seminal fluid contains enhancers and inhibitors of HIV infection (Münch et al., 2007; Sabatté et al., 2011) that can drive cytokine responses in the FRT that mediate chemotaxis of HIV target cells, possibly amplifying infection (Robertson, 2005). It could be valuable to reproduce these aspects of exposure to HIV that are specific to copulation in model systems. Our animal model of HIV infection employs EcoHIV, chimeric HIV clones in which the gp120 coding region is replaced by the coding region of the ecotropic murine leukemia virus (MLV) envelope, switching the viral tropism from human to rodent (Potash et al., 2005); all other genes and functions in EcoHIV are derived from HIV. Two viruses have been constructed on Subtype B and Subtype D HIV backbones, EcoHIV/NL4-3 and EcoHIV/ NDK, respectively. After inoculation into conventional mice, the viruses infect lymphocytes and macrophages; antiretrovirals, HIV DNA vaccination and anti-EcoHIV CD8+ T cells each can control this virus replication in mice (Hadas et al., 2007; Kelschenbach et al., 2012; Roshorm et al., 2009; Saini et al., 2007). Disease Models & Mechanisms 6, 1292-1298 (2013) doi:10.1242/dmm.012617