From the Literature

The number of known HTLVs has doubled with the identification of HTLV-3 and HTLV-4 in recent years. HTLVs are d-retroviruses that arose from simian retroviruses (STLV). The entire group of viruses, both human and simian, are now termed primate T-lymphotropic viruses (PTLV). PTLVs are numbered 1–4 and each is comprised of the corresponding HTLV and STLV—thus, PTLV-2 is made up of HTLV-2 and its ancestor, STLV-2 (the simian counterpart of HTLV-4 has not yet been identified). HTLV-1 and HTLV-2 are widespread in the human population. HTLV-1 infection is associated with human disease in !5% of those infected, with the most frequent manifestations being human T-cell leukemia/lymphoma, myelopathy, and various inflammatory disorders. HTLV-2 may be associated with a myelopathic disorder. The distribution and potential disease associations of HTLV-3 and HTLV-4 are as yet unknown. The progenitor of HTLV-3, STLV-3, is broadly distributed in Africa, but only 3 strains of HTLV-3 have been identified to date—all in Cameroon. The only isolation of HTLV-4 so far has been from a primate hunter in the Cameroonian forest but, in contrast to the other HTLVs, the simian counterpart has not yet been identified. Phylogenetic analysis of the HTLV-4 genome sequence demonstrated it to be distinct and equidistant from the other HTLVs, with only 62%-71% identity at the nucleotide level. The genome contains important sequences necessary for viral expression, including potential oncogenesis. Molecular dating indicates that the HTLV4 lineage split off from a progenitor of PLTV-2 approximately 200,000 years ago, a time that more or less corresponds to the appearance of Homo sapiens 200,000– 400,000 years ago. The continued detection of previously unknown human viruses and retroviruses is opening a new chapter in our understanding of human health and disease. Whether HTLV-4 and/or HTLV-3 play an important role remains to be seen.