Interdisciplinary Graduate Programs Symposium
2011 OSU Molecular Life Sciences
Interdisciplinary Graduate Programs Symposium
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Poster abstracts
Abstract:
Human T-cell leukemia Virus type I (HTLV-1) and II (HTLV-2) are closely related but pathogenic distinct human retroviruses. In HTLV-1, the anti-sense strand of viral genome encodes HBZ, a nuclear basic leucine zipper (bZIP) protein which is important for establishing HTLV-1 associated disease. Recently, an anti-sense viral protein (APH-2) was characterized in HTLV-2. Like HBZ, APH-2 interacts with cyclic adenosine monophosphate-response element binding protein (CREB) despite the lack of a leucine zipper domain and down-regulates tax-mediated viral transcription. In this study, we investigated the functional role of APH-2 in HTLV-2 mediated immortalization of primary T-lymphocytes in vitro and in HTLV-2 infection in vivo. APH-2 mutant viruses are generated and evaluated for viral gene expression, immortalization capacity and viral survival and persistence. In vitro, the immortalization capacity of APH-2 mutant viruses is indistinguishable from wild type virus indicating that APH-2 is dispensable for viral infection and cellular transformation. In vivo, rabbits inoculated with APH-2 mutant viruses displayed an increased antibody response to selected viral gene products and a higher proviral load in peripheral blood mononuclear cells (PBMCs) as compared to wild type HTLV-2 inoculated rabbits, which is due to the fact that APH-2 mutant viruses undergo a higher viral gene expression and replication because of a loss of APH-2 regulatory control on viral transcription. Our findings indicate that APH-2 is also dispensable for viral survival and persistence in rabbit animal model. This study demonstrates that antisense proteins of HTLV-1 and HTLV-2 play different roles in vivo, which provides fundamental insights into the distinct pathogenic property of two viruses.
Keywords: retrovirus, antisense, immortalization
