Abstract
The 3′ end of the human T-cell leukemia/lymphoma virus type-1 (HTLV-1) genome contains four overlapping open reading frames (ORF) that encode regulatory proteins. Here, we review current knowledge of HTLV-1 orf-I and orf-II protein products. Singly spliced mRNA from orf-I encodes p12, which can be proteolytically cleaved to generate p8, while differential splicing of mRNA from orf-II results in production of p13 and p30. These proteins have been demonstrated to modulate transcription, apoptosis, host cell activation and proliferation, virus infectivity and transmission, and host immune responses. Though these proteins are not essential for virus replication in vitro, p8, p12, p13, and p30 have an important role in the establishment and maintenance of HTLV-1 infection in vivo.
Highlights
Human T-cell leukemia/lymphoma virus type-1 (HTLV-1) is an oncogenic retrovirus first discovered in 1980 in T-cells of a patient with cutaneous T-cell lymphoma [1,2]
CTLs and antibodies that recognize orf-II peptides can be detected in human T-cell leukemia/lymphoma virus type-1 (HTLV-1)-infected individuals, suggesting that p13 may have an important role in vivo [104,117]
As transcription of the provirus could lead to antigen presentation and immune recognition, it is necessary for HTLV-1 to maintain low levels of virus replication
Summary
Human T-cell leukemia/lymphoma virus type-1 (HTLV-1) is an oncogenic retrovirus first discovered in 1980 in T-cells of a patient with cutaneous T-cell lymphoma [1,2]. Further work in the rabbit model showed reversion of HTLV-1 clones lacking p30 to the wildtype p30-expressing virus, suggesting the importance of p30 to HTLV-1 viral persistence [34] In these early studies the HTLV-1 clones that were used contained a frameshift that affected hbz, making it unclear as to whether these effects were due to the loss of hbz or orf-I and orf-II-encoded proteins. The orf-I and orf-II-encoded proteins are able to modulate a diverse range of viral and cellular mechanisms including transcriptional regulation, mitochondrial function, cell cycle progression, host cell activation and proliferation, apoptosis, virus infectivity and transmission, and host immune responses. Though these proteins are not essential for virus replication in vitro, p8, 12,. The p13 protein is translated from singly spliced mRNA transcribed from orf-II and corresponds to the carboxyl terminus of p30
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