The assignee for this patent, patent number 8530431, is
Reporters obtained the following quote from the background information supplied by the inventors: "The Human Immunodeficiency Virus (HIV) trans-activator of transcription (Tat) is a variable RNA binding peptide of 86 to 110 amino acids in length that is encoded on two separate exons of the HIV genome. Tat is highly conserved among all human lentiviruses and is essential for viral replication. When lentivirus Tat binds to the TAR (trans-activation responsive) RNA region, transcription (conversion of viral RNA to DNA then to messenger RNA) levels increase significantly. It has been demonstrated that Tat increases viral RNA transcription and it has been proposed that Tat may initiate apoptosis (programmed cell death) in T4 cells and macrophages (a key part of the body's immune surveillance system for HIV infection) and possibly stimulates the over production of alpha interferon (.alpha.-interferon is a well established immunosuppressive cytokine).
"Extracellular Tat's presence early in the course of HIV infection could reduce a patient's immune response, giving the virus an advantage over the host. Furthermore, the direct destruction of T4 cells and induction of .alpha.-interferon production could help explain the lack of a robust cellular immune response seen in Acquired Immunodeficiency Syndrome (AIDS) patients, as well as accounting for the initial profound immunosuppression.
"However, Tat protein isolated from HIV-infected long term non-progressors (LTNP) is different from C-Tat found in AIDS patents. The Tat protein found in LTNP is capable of trans-activating viral RNA, however, LTNP Tat (designated herein after as IS-Tat for immunostimulatory Tat) does not induce apoptosis in T4 cells or macrophages and is not immunosuppressive. Moreover, T4 cells infected ex vivo with HIV isolated from LTNP (such cell lines are designated Tat TcL) can result in the over expression of IS-Tat proteins, often to the virtual exclusion of other viral proteins, that are strongly growth promoting rather than pro-apoptotic. The Tat genes cloned from these Tat TcLs reveal sequence variations in two Tat regions, at the amino terminus and within the first part of the second exon. These surprising discoveries could help explain why HIV infected LTNP T4 cells do not die off at the staggering rate seen in HIV infected individuals that progress to AIDS.
"Additionally, variants of Tat are found in lentiviruses which infect monkey species yet do not result in the development of immunodeficiency and epidemic infection. These variant Tat proteins direct monocyte differentiation into dendritic cells (DCs) which stimulate cytotoxic T lymphocyte (CTL) responses. These simian Tat variants, and other Tat variants that are not immunosuppressive, have been termed attenuated or immunostimulatory Tat (IS-Tat).
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