Role of retrovirus-induced transactivator proteins in neuroinflammatory disease

Abstract

Human immunodeficiency virus type I (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1) lead to acquired immunodeficiency syndrome (AIDS) and adult T-cell leukemia, respectively, and these viruses have also been identified as the etiologic agents of HIV-associated neurocognitive disorders (HAND) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Pathogenic processes associated with these diseases are due to HIV-1 and HTLV-1 infecting not only cells of the host immune system but also cells of the central nervous system (CNS). For each of these viruses (HIV-1 and HTLV-1), the major viral regulatory proteins, Tat and Tax, respectively, have been shown to be implicated as extracellular neurotoxic proteins. This chapter will provide an overview of the structure and function of Tat and Tax and describe their role in viral replication focusing on their interaction with their viral promoters. Information will then be presented that describes known modifications of these important regulatory and neurotoxic proteins and the current understanding with respect to how these proteins are secreted into the extracellular environment. Please check if edit to sentence starting The specific roles is okay. The specific roles that Tat and Tax play as extracellular proteins especially their role in neuropathogenesis are discussed with a focus on comparing their functional similarities and differences. Finally, the review will discuss the immune response in the CNS with respect to these two essential viral transactivator proteins.