Molecular Evidence of Human T‑Cell Leukemia Virus Type 1 Transmission by Needlestick Injury in Healthcare Workers.

Human T‑cell leukemia virus type 1 (HTLV‑1) is a retrovirus that spreads primarily through cell-to-cell transmission. Occupational transmission of HTLV-1 by needlestick injury is considered exceedingly rare, with no reported molecularly confirmed cases. We report two healthcare workers who experienced accidental needlestick injuries while caring for patients seropositive for HTLV‑1 and subsequently seroconverted. Full‑length HTLV‑1 proviral sequencing revealed complete nucleotide identity between source patients and infected nurses. These strains belonged to the HTLV-1 subtype 1a Japanese subgroup but were distinct from 315 previously registered strains. Proviral integration site analysis demonstrated nonoverlapping integration profiles between source patients and healthcare workers, providing direct evidence of de novo HTLV‑1 infection rather than expansion of transferred infected cells. Longitudinal analysis in one case showed dynamic clonal turnover between 5 and 14 months after transmission; > 90% of infected-cell clones were replaced, although the proviral load remained stable and low. Serological profiling revealed transiently elevated immunoglobulin M responses to Gag p19 peptides during early infection, followed by gradual immunoglobulin G maturation. These findings provide the first molecular confirmation of HTLV‑1 transmission via needlestick injury resulting in de novo infection, revealing an under-recognized occupational exposure route and supporting reconsideration of post-exposure testing strategies, particularly in endemic regions.