Noncoding RNAs in Retrovirus Replication

Although a limited percentage of the genome produces proteins, approximately 90% is transcribed, indicating important roles for noncoding RNA (ncRNA). It is now known that these ncRNAs have a multitude of cellular functions ranging from the regulation of gene expression to roles as structural elements in ribonucleoprotein complexes. ncRNA is also represented at nearly every step of viral life cycles. This chapter will focus on ncRNAs of both host and viral origin and their roles in retroviral life cycles. Cellular ncRNA represents a significant portion of material packaged into retroviral virions and includes transfer RNAs, 7SL RNA, U RNA, and vault RNA. Initially thought to be random packaging events, these host RNAs are now proposed to contribute to viral assembly and infectivity. Within the cell, long ncRNA and endogenous retroviruses have been found to regulate aspects of the retroviral life cycle in diverse ways. Additionally, the HIV-1 transactivating response element RNA is thought to impact viral infection beyond the well-characterized role as a transcription activator. RNA interference, thought to be an early version of the innate immune response to viral infection, can still be observed in plants and invertebrates today. The ability of retroviral infection to manipulate the host RNAi pathway is described here. Finally, RNA-based therapies, including gene editing approaches, are being explored as antiretroviral treatments and are discussed.