Cryo-ET Studies of HTLV-1
There are approximately 20 million people infected by HTLV-1 worldwide. HTLV-1 infection can result in a number of severe disorders including adult T cell leukemia/lymphoma (ATLL) as well as HTLV-1 associated myelopthy/tropical paraparesis (HAM/TSP). Despite its association with cancer and significant impact on human health, many of the details regarding the replication, assembly and fundamental virus particle structure remain poorly understood.
Previous molecular analyses of HTLV-1 replication have been severely hampered by the fragility of HTLV-1 proviral sequences as well as the low levels of viral replication in tissue culture. These researchers had sought to overcome this critical barrier by creating an experimental model system that is amenable to successfully and efficiently analyze HTLV-1 assembly. They are now employing cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) to study the structures of HTLV-1 immature and mature particles, as well as authentic viruses. Specifically, they will determine the global organization of HTLV-1 immature Gag lattice and the molecular structure of the mature capsid lattice. By comparing with the available HIV-1 immature and mature particle structures, they would like to further examine if the architectures of immature Gag lattice and the fundamental principles of mature capsid lattice are conserved among these retroviruses. Moreover, they would like to detect the critical molecular contacts on Gag protein that are required for viral assembly and the specific regions that undergo conformational changes during maturation. The results of this work will be useful to uncover the molecular mechanism of HTLV-1 assembly and maturation, and may inform new therapeutic strategies.
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