Human T-cell leukemia virus type 2 post-transcriptional control protein p28 is required for viral infectivity and persistence in vivo

In this study, we investigated the functional significance of p28 in HTLV-2 infection, proliferation, and immortaliztion of primary T-cells in culture, and viral survival in an infectious rabbit animal model. An HTLV-2 p28 knockout virus (HTLV-2Δp28) was generated and evaluated. Infectivity and immortalization capacity of HTLV-2Δp28 in vitro was indistinguishable from wild type HTLV-2. In contrast, we showed that viral replication was severely attenuated in rabbits inoculated with HTLV-2Δp28 and the mutant virus failed to establish persistent infection.We provide direct evidence that p28 is dispensable for viral replication and cellular immortalization of primary T-lymphocytes in cell culture. However, our data indicate that p28 function is critical for viral survival in vivo. Our results are consistent with the hypothesis that p28 repression of Tax and Rex-mediated viral gene expression may facilitate survival of these cells by down-modulating overall viral gene expression.The human T-cell leukemia viruses (HTLV types 1–4) are classified as complex retroviruses and members of the genus Deltaretrovirus [1]. HTLV-1 and HTLV-2 infections are the most prevalent worldwide, whereas infections with HTLV-3 and HTLV-4 were discovered only recently in a very limited number of individuals in Africa [2,3]. Although people infected with HTLV have a persistent antiviral immune response, these patients fail to clear virally infected cells. A small percentage of HTLV-1-infected individuals develop adult T-cell leukemia (ATL), a CD4+ lymphocyte malignancy, and various lymphocyte-mediated inflammatory diseases such as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) [4-7]. However, only a few cases of atypical hairy cell leukemia or neurologic disease have been associated with HTLV-2 infection [8-12]. HTLV-1 and HTLV-2 have the capacity to promote T-lymphocyte growth both in cell culture and in infected individuals; however, the mechanism by which the virus persis