Retroviruses and Insights into Cancer: Retroviral Regulatory/Accessory Genes and Cancer

Abstract

The distinguishing feature that separates simple and complex retroviruses is that in addition to the structural and enzymatic gene products, complex retroviruses have regulatory and accessory genes that encode for proteins that perform a multitude of functions. Extensive research has been performed to elucidate the functional role that these gene products play in the viral-life cycle and their potential contribution to pathogenesis. This chapter focuses on the biological properties of regulatory and/or accessory genes from two very distinct human retroviruses: human T-cell leukemia virus type 1 (HTLV-1) and human endogenous retrovirus (HERV)-K. HTLV-1 infection is associated with leukemia/lymphoma and a variety of immune-mediated disorders. We will discuss the HTLV-1 Tax oncoprotein and the novel minus strand-encoded leucine zipper-gene product, HBZ, with emphasis on their contribution to deregulation of transcription, cellular signal-transduction pathways, and cellular checkpoints. The expression of these gene products may create an environment favorable for cellular transformation and the development and maintenance of a virus-induced disease. HERVs have been implicated in the etiology of multiple types of diseases, such as autoimmune diseases, neurological disorders, and several forms of cancer. The remaining part of the chapter will focus on Rec (formally known as cORF) and the Np9 ­regulatory proteins of HERV-K, as well as the association of these proteins with cancer development.