Human T cell leukemia virus type 1 (HTLV-1) was the first discovered pathogenic human retrovirus. HTLV-1, the etiologic agent of adult T cell leukemia (ATL), encodes a viral oncoprotein, Tax that is necessary and sufficient for viral transformation. HTLV-1 is the prototypic member of a human retrovirus family that also includes HTLV-2, which has not been definitively linked to any human disease. HTLV-1 and -2 are closely related to the simian T cell leukemia viruses, STLV-1 and -2, respectively. In 2005, the human homologue (HTLV-3) of a third simian retrovirus group, STLV-3, was independently isolated twice from Central African primate hunters, and a third independent isolation of HTLV-3 from humans was recently reported. The genome of the HTLV-3 (2026ND) isolate, in particular the Tax gene, is more closely related to HTLV-1 than to HTLV-2, especially in domains that are thought to be important for transformation. The broad distribution of STLV-3 in African primates and independent isolation of HTLV-3 multiple times from humans, suggest that HTLV-3 is prevalent in Africa. An additional human retrovirus, HTLV-4, was also isolated from an African primate hunter in 2005 and is distinct from all known HTLVs and STLVs. In contrast to HTLV-3, the HTLV-4 genome, in particular the Tax gene, is more closely related to HTLV-2 than to HTLV-1. This application is based on the hypothesis that the HTLV-3 Tax protein possesses oncogenic properties while the HTLV- 4 Tax protein does not. This hypothesis will be investigated in two specific aims that focus on determining the transforming potential, transcriptional activity, and protein interacting partners of the HTLV-3 and HTLV-4 Tax proteins. Since HTLV-3 and HTLV-4 appear to be emerging as new human retroviruses, it is critical that we determine the potential of these viruses to cause disease in humans.
Viruses are important causes of cancer in animals and in humans. One particular virus called HTLV-1 is known to cause a type of leukemia in humans. Two new viruses were recently found in humans and these new viruses are very closely related to HTLV-1. Therefore, we think that at least one of the new viruses may cause cancer in humans. HTLV-1 makes a protein called Tax that is necessary for the virus to cause cancer. We plan to compare the Tax protein made by HTLV-1, with the Tax protein made by each of the two new viruses so that we can determine whether the new viruses are likely to cause human cancer. ? ? ?
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