Human T-cell leukemia virus type 1 integrase (HTLV-1 IN)

Human T-cell leukemia virus type 1 (HTLV-1) integrase is a critical viral enzyme responsible for incorporating the reverse-transcribed viral DNA into the host cell genome, a process essential for viral replication and lifelong persistence (Cereseto et al., 2023, PubMed: 37402145). The enzyme functions through two distinct catalytic steps: 3'-end processing, where two nucleotides are removed from the viral DNA ends, and strand transfer, which covalently joins the viral DNA to host chromosomal DNA (Maertens, 2016, PubMed: 27158052). HTLV-1 integrase is a key therapeutic target because its inhibition prevents the formation of the provirus, thereby blocking the establishment of infection in new cells. While drugs developed for HIV-1 integrase, known as integrase strand transfer inhibitors (INSTIs) like Raltegravir and Dolutegravir, show potent in vitro activity against HTLV-1 IN, their clinical utility in treating HTLV-1-associated diseases like Adult T-cell leukemia (ATL) or HAM/TSP remains a subject of ongoing clinical investigation (Leal et al., 2015, PubMed: 26113619). The structural homology between HTLV-1 and HIV-1 integrases allows for the repurposing of existing antiretrovirals, though differences in the intasome structure may affect drug binding affinity and resistance profiles (Barski et al., 2021, PubMed: 33504825).

Other names

HTLV-1 integraseHuman T-lymphotropic virus 1 integrasePol protein integrase domainRetroviral integrase

Integrase strand transfer inhibitor (INSTI)