start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=9
article-no=
start-page=e0086926
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2026
dt-pub=20260901
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Combinations of long terminal repeat and tax protein substitutions influence bovine leukemia virus transmission through altered viral productivity
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Bovine leukemia virus (BLV) infection imposes a substantial economic burden on the global cattle industry. Although proviral load (PVL) in blood influences transmission, the effects of viral genetic variations, including the high viral production-associated long terminal repeat (LTR) substitution at nucleotide position 175 (LTR175), on herd-level dynamics remain unclear. This study investigated the effects of specific substitutions on the regulation of viral productivity and transmission. Longitudinal monitoring of a single farm (herd size: 50–68 cows; 438 samples collected) over a 7-year period revealed that viral strains carrying cytosine at LTR175 (LTR175C) significantly increased in frequency, becoming dominant over wild-type strains carrying thymidine. In contrast, amino acid substitutions in the Tax protein at positions 69 (Tax69) and 73 (Tax73) modified viral transactivation independent of LTR175. Structural modeling via AlphaFold2 predicted that Tax69 and Tax73 mutations alter protein properties, suggesting modulation of transactivation activity. Consistent with this prediction, in vitro assays confirmed that the substitutions modified viral production by regulating transactivation independent of LTR175. Moreover, high viral-productivity haplotypes containing LTR175C and Tax73Q (glutamine at amino acid residue 73) exhibited a transmission advantage within the herd, even when host PVL levels were not significantly elevated. These findings suggest that cellular-level viral productivity is one of the key determinants of transmission fitness. Overall, this study revealed a regulatory interaction between the LTR and Tax protein that optimizes viral spread and highlights the need for control strategies that account for viral genetic substitutions.
en-copyright=
kn-copyright=

en-aut-name=MurakamiHironobu
en-aut-sei=Murakami
en-aut-mei=Hironobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SatoReiichiro
en-aut-sei=Sato
en-aut-mei=Reiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=UchiyamaJumpei
en-aut-sei=Uchiyama
en-aut-mei=Jumpei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SogawaKazuyuki
en-aut-sei=Sogawa
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=IshidaHiroho
en-aut-sei=Ishida
en-aut-mei=Hiroho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NagaiMakoto
en-aut-sei=Nagai
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=School of Veterinary Medicine, Azabu University
kn-affil=

affil-num=2
en-affil=Graduate School of Medicine and Veterinary Medicine, University of Miyazaki
kn-affil=

affil-num=3
en-affil=Department of Infectious Diseases, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=School of Life and EnvironmentaScience, Azabu University
kn-affil=

affil-num=5
en-affil=School of Veterinary Medicine, Azabu University
kn-affil=

affil-num=6
en-affil=School of Veterinary Medicine, Azabu University
kn-affil=
en-keyword=bovine leukemia virus
kn-keyword=bovine leukemia virus
en-keyword=substitution
kn-keyword=substitution
en-keyword=transmission
kn-keyword=transmission
en-keyword=haplotype
kn-keyword=haplotype
en-keyword=molecular clone
kn-keyword=molecular clone
en-keyword=proviral load
kn-keyword=proviral load
en-keyword=reverse genetics
kn-keyword=reverse genetics
END