Year: 2025
Type: article
Abstract: Human T-cell Leukaemia Virus type 1 (HTLV-1) is an untreatable retrovirus that causes lethal malignancies and degenerative inflammatory conditions. Effective treatments have been delayed by substantial gaps in our knowledge of the fundamental virology, especially when compared to the closely related virus, HIV. A recently developed and highly effective anti-HIV strategy is to target the virus with drugs that interfere with capsid integrity and interactions with the host. Importantly, the first in-class anti-capsid drug approved, lenacapavir, can provide long-acting pre-exposure prophylaxis. Such a property would provide a means to prevent the transmission of HTLV-1, but its capsid has not previously been considered as a drug target. Here we describe high-resolution crystal structures of the HTLV-1 capsid protein, define essential lattice interfaces, and identify a distinct ligand-binding pocket. We show that this pocket is essential for virus infectivity, providing a potential target for future anti-capsid drug development.
Source: Nature Communications
Institutions: UNSW Sydney, EMBL Australia
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Australian Nuclear Science and Technology Organisation, Wellcome Trust, Analytical Center for the Government of the Russian Federation, Australian Cancer Research Foundation, Australian Synchrotron, University of New South Wales, Medical Research Council, National Health and Medical Research Council
Awards: Understanding how viruses overcome the nuclear pore complex, the gatekeeper of genomic access, What is special about pandemic HIV-1? How capsid cofactor interactions regulate DNA synthesis, innate immune detection and pandemic potential, What is special about pandemic HIV-1? How capsid cofactor interactions regulate DNA synthesis, innate immune detection and pandemic potential
OpenAlex ID: W4416985665