Chapter 32 Human Retroviruses, HIV and HTLV

Abstract

INTRODUCTION Retroviruses were for many decades well known causative agents of leukemias, lymphomas, other cancers, or chronic inflammations in various animal species. The discovery of the first human retrovirus, human T-cell leukemia virus (now renamed human T-lymphotropic retrovirus type 1; HTLV-1) was reported in 1980 (Poiesz et al., 1981). HTLV-1 was soon identified as the causative agent of adult T-cell leukemia/lymphoma (ATLL), a rapidly progressing cancer of CD4+ T lymphocytes first described in southeastern Japan (Takatsuki et al., 1977). Knowledge gained from HTLV-1 research was important for the subsequent detection of other human retroviruses, first the related HTLV-2 (Kalyanaraman et al., 1982). Soon thereafter, human immunodeficiency virus (HIV)-1 was for the first time isolated from a patient with an early stage of the newly recognized acquired immunodeficiency syndrome (AIDS) (Barre-Sinoussi et al., 1983). Two years later, a second AIDS-causing virus, HIV-2, was discovered (Clavel et al., 1986a). Investigations among nonhuman primates showed a wide distribution of viruses resembling both the HTLV and, respectively, HIV groups of retroviruses. Simian Tlymphotropic retrovirus type (STLV)-1 and STLV-2, simian counterparts of HTLV-1 and HTLV-2, were identified. STLV-3 forms a third group of lymphotropic viruses infecting various African monkey species. HTLV-3, a counterpart of STLV-3 in man, was recently detected in African pygmies (Calattini et al., 2005; Wolfe et al., 2005; Calattini et al., 2006; Switzer et al., 2006). A further HTLV forming a fourth group, HTLV-4, also has been reported (Wolfe et al., 2005). Together, these viruses now constitute four groups of primate T-lymphotropic retroviruses (PTLV-1, -2, -3, -4), with representatives in both simians (STLV) and humans (HTLV). Similarly, both HIV-1 and HIV-2 were shown to originate from primate lentiviruses collectively named simian immunodeficiency viruses (SIV). Other reports of retrovirus infections in humans include isolated cases in which foamy retroviruses (Switzer et al., 2004), simian type-D retrovirus (Lerche et al., 2001) or SIV (Khabbaz et al., 1994) were found in humans as a result of direct cross-species nosocomial transmission from monkeys to caretakers. Transmission of such agents through close and repeated exposure to wild monkeys, for example in bushmeat hunters, also has been reported (Wolfe et al., 2004). Transmission of animal retroviruses to man may not be restricted to viruses of primate origin. Of interest are the recent identification of a betaretrovirus closely related to mouse mammary tumor virus (MMTV) in patients with the autoimmune disease primary biliary cirrhosis (Mason et al., 2004; Xu et al., 2004) and the isolation of an infectious xenotropic murine retrovirus (XMRV) in a form of familial prostate cancer characterized by homozygosity for a reduced activity variant of the antiviral enzyme RNase L (Dong et al., 2007; Fan, 2007). On the other hand, an earlier claim of a novel human retrovirus, has received no follow-up confirmation. This relates to the "human retrovirus 5" (HRV-5), which now has been identified as a rabbit endogenous retrovirus contaminant, RERV-H (Griffiths et al., 2002). An overview of the currently known exogenous human retroviruses and the diseases associated with them is shown in Table 1. In addition, the question whether endogenous human retroviruses might contribute to human autoimmune disease like multiple sclerosis, Sjogren's syndrome, systemic lupus erythematosus and others remains unresolved (Perron et al., 2005; Sander et al., 2005).