Abstract
Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia-lymphoma (ATL) and inflammatory diseases including HTLV-1-associated myelopathy (HAM). A remarkable feature of HTLV-1 is that this virus transmits primarily through cell-to-cell contact. HTLV-1 increases the number of infected cells in vivo to ensure its survival and transmission. Therefore, survival of HTLV-1-infected cells in vivo is very critical for transmission under the host immune surveillance. HTLV-1 possesses multiple strategies to evade host immune responses. Among viral genes, Tax and HTLV-1 bZIP factor (HBZ) play crucial roles in the proliferation of infected cells and the subsequent development of ATL. Although Tax strongly activates the NF-kB pathway, the immunogenicity of Tax is very high; it is a major target of cytotoxic T lymphocytes. Therefore, the virus minimizes Tax production, expressing it only intermittently in vivo. On the other hand, the immunogenicity of HBZ is low, and its expression is maintained in all ATL cases. HBZ transforms the immunophenotype of infected cells into regulatory T cell-like (CD4+ CD25+ CCR4+ TIGIT+ Foxp3+), and promotes the production of immunosuppressive cytokines. Furthermore, HBZ mRNA not only encodes the protein but also functions itself like long non-coding RNA. As a result, Tax and HBZ enable long-term escape from host immunity, persistent infection, and proliferation of infected cells. Here, we review the viral strategies to counteract to host immune surveillance system.
Highlights
Human T-cell leukemia virus type 1 (HTLV-1) causes the neoplastic disease, adult T-cell leukemia-lymphoma (ATL), and various inflammatory diseases including HTLV-1 associated myelopathy (HAM) and uveitis (HU) [1]
These findings indicate that HTLV-1 bZIP factor (HBZ) can induce clonal proliferation of HTLV-1 infected cells and cause ATL even without Tax [18]
Combining HBZ mediated enhancement of IL-10 production with modulated signaling from the IL-10 receptor seems to be a clever strategy of HTLV-1 – a strategy that enables both proliferation of infected T cells and suppression of host immune responses
Summary
Human T-cell leukemia virus type 1 (HTLV-1) causes the neoplastic disease, adult T-cell leukemia-lymphoma (ATL), and various inflammatory diseases including HTLV-1 associated myelopathy (HAM) and uveitis (HU) [1]. HTLV-1 increases the number of infected T cells in vivo by causing them to proliferate [7]. Clonal proliferation of infected T cells with non-sense mutations of tax is found in carriers and ATL cases [15,16,17]. These findings indicate that HBZ can induce clonal proliferation of HTLV-1 infected cells and cause ATL even without Tax [18]. Transient Tax expression generates vigorously proliferating cells, and may be a viral mechanism for maintaining the infected cell population This type of Tax expression is observed in about half of ATL cases [18]
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