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PTLV-1 encodes multiple proteins from overlapping open reading frames (ORFs) in the pX region. This study aims to characterize the conservation of these proteins in different PTLV-1 subtypes and their role in pathogenesis. For the first time, we report the full-length proviral sequence of an STLV-1 strain isolated from chimpanzee and African green monkey. Phylogenetic analysis reveals high conservation of the accessory proteins p12, p30, and p13 in the HTLV-1a subtype. Conversely, some African PTLV-1 subtypes exhibit loss of ORFs for p12 or p13. For Asian subtypes, simian strains often lack p12, p13, or p30 proteins, whereas human strains retain the ORFs of p30 and p13 but not p12. To assess the infectivity of a simian strain of PTLV-1 lacking ORFs for p12, p13, and p30, we constructed a molecular clone from a naturally infected Japanese macaque (Mfu: <jats:italic>Macaca fuscata<\/jats:italic>) and compared it with HTLV-1a. Using a reporter assay and ELISA, we found similar infectivity to Jurkat T cells; however, STLV-1 Mfu exhibited impaired infectivity in the monocytic cell line THP-1. Additionally, despite the conservation of the HTLV-1\/STLV-1 bZIP factor (HBZ\/SBZ) ORFs, HBZ\/SBZ proteins derived from HTLV-1a and African PTLV-1 subtypes induce significantly higher activation of the TGF-\u03b2\/Smad signaling pathway than those from Asian subtypes. Collectively, our findings suggest that the acquisition of the accessory proteins by PTLV-1 subtypes potentially confers an advantageous adaptation of PTLV-1 during infection in apes, including humans. Moreover, among PTLV-1 strains, HBZ\/SBZ had varying degrees of activity on the TGF-\u03b2\/Smad pathway; this fact underscores the complex interplay between viral proteins and host signaling pathways, possibly influencing the viral pathogenicity in different species.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013158","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T18:06:56Z","timestamp":1746814016000},"page":"e1013158","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Evolution of primate T-cell leukemia virus type 1 accessory genes and functional divergence of its antisense proteins"],"prefix":"10.1371","volume":"21","author":[{"given":"Osama","family":"Hussein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Mahgoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Shichijo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Tanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Akari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7939-2080","authenticated-orcid":true,"given":"Jun-ichirou","family":"Yasunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ppat.1013158.ref001","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nrc2111","article-title":"Human 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