R EVIEWS TRENDS IN MICROBIOLOGY 477 VOL. 6 NO. 12 DECEMBER 1998 0966-842X/98/$ - see front matter © 1998 Elsevier Science. All rights reserved. PII: S0966-842X(98)01406-1 T he human T-cell lympho- tropic viruses HTLV-I and HTLV-II are retro- viruses. HTLV-I is known to be associated with lymphoma, leukemia and some neurologi- cal diseases 1 . The lifetime risk of HTLV-I-associated diseases is 5–10% (Refs 1,2), with a 1–5% chance of developing adult T-cell leukemia (ATL) and a 1% chance of develop- ing tropical spastic paraparesis (TSP) [also known as HTLV-I- associated myelopathy (HAM)]. HTLV-II also seems to be asso- ciated with HAM/TSP-like dis- eases, but to a much lesser extent 3,4 . The simian equivalent, STLV-I, infects most Old World primate species 5 and is also associated with lymphoma and leukemia 6 . Recently, two new STLVs have been found in African non-human primates: STLV-L in a hamadryas baboon (Papio hamadryas) from Eritrea 7–9 , and STLV-PP (now called STLV-II) in bonobos (Pan paniscus) from the Democratic Republic of Congo 10–14 . Together, these human and simian viruses are known as primate T-cell lymphotropic viruses (PTLVs). Serology and epidemiology of PTLV-I PTLV transmission is not very efficient and only occurs by sexual contact, maternal transmission, mainly through breast-feeding, and blood-to-blood contact, such as needle sharing. In endemic popu- lations, husband-to-wife and mother-to-child trans- mission result in familial clustering of HTLV-I infec- tion 15–17 . The serological identification of HTLV-I and HTLV-II is usually based on reactivity in a west- ern blot towards HTLV-I antigens, using separate type-specific peptides to differentiate between the two types. However, large amounts of reactive sera remain indeterminate 18 and are consequently discarded by blood banks. In particular, it is not clear whether the indeterminate patterns observed with HTLV-I- based western blots reflect real viral infections. For example, indeterminate patterns resulting from Gag reactivity, which are frequently observed in samples from tropical areas, might be related to other pathogens, such as Plasmodium falciparum, or to autoimmuno- logical reactions 19 . Most of the western blot indeterminates are PCR negative and are thus assumed to be uninfected, al- though some can be identified as being infected with HTLV-I or HTLV-II (Refs 18,20). Their indeterminate serologi- cal reactivity could result from infection with divergent strains or from a poor immune response 20,21 . Epidemiological studies have revealed that the endemic foci of HTLV-I are scattered across Asia, Africa, America and Oceania 2 . The areas with the highest prevalence are Japan and equatorial Africa, and the lowest prevalence is found in Europe. Origins of PTLV-I HTLV is a complex retrovirus consisting of a long terminal repeat (LTR) promoter, structural (gag and env) and enzymatic (pro and pol) coding regions, and regulatory (tax and rex) and accessory coding re- gions. The accessory proteins differ between PTLV types I, II and L (Refs 8,22,23), and even between subtypes 24,25 . HTLV has several remarkable features that make it an exceptional tool and subject for phylogenetic analysis. First, HTLV is maintained in an endemic population, mainly by mother-to-child transmission, owing to limited horizontal transmission and the low mortality rate. In this way, it acts as a genetic marker for some populations 16 . Second, compared with HIV, HTLV has a very stable genome. The LTR of HTLV-II in drug users has been estimated to have ≈10 -4 –10 -5 nucleotide substitutions per site per year 26 , making it one of the slowest evolving RNA viruses; the normal evolutionary rate of RNA viruses is ≈10 -2 –10 -4 nu- cleotide substitutions per site per year 27 . The evo- lutionary rate of HTLV-I is probably similar or, per- haps, lower 15 . The slow evolution of these viruses might partly result from the fact that the proviral load is mainly maintained in the host by clonal expansion of infected cells, with only a limited contribution from active viral replication 28,29 . The higher fidelity of At least four, and possibly six, molecular subtypes of human T-cell lymphotropic virus type I (HTLV-I) exist: one is confined to Melanesia/Australia, one is ubiquitous, and the others are found only in Africa. Molecular epidemiology suggests that all subtypes arose from separate interspecies transmissions from simians to humans. A-M. Vandamme*, M. Salemi and J. Desmyter are in the Rega Institute for Medical Research and University Hospitals, Katholieke Universiteit Leuven, Minderboedersstraat 10, B-3000 Leuven, Belgium. *tel: +32 16 332160, fax: +32 16 332131, e-mail: vandamme@uz.kuleuven.ac.be The simian origins of the pathogenic human T-cell lymphotropic virus type I Anne-Mieke Vandamme, Marco Salemi and Jan Desmyter