Role of the nucleolus in HIV infection and therapy

Abstract

HIV (human immunodeficiency virus), the etiological agent of AIDS (acquired immunodeficiency syndrome), is the most studied virus internationally. Treatment and prevention of AIDS-induced opportunistic infections are available with antiretroviral therapy (ART); however, HIV infection is incurable because of the latent integrative states of the virus and the inaccuracy of reverse transcription, which gives rise to HIV microvariants and quasispecies. HIV variants escape recognition and build resistance against current treatments. We have shown that potential therapeutic interventions involve nucleolar- trafficking small RNAs, which include U16 small nucleolar RNA (snoRNA) hammerhead ribozymes (U16Rz), U16 transactivation response (U16TAR) decoys, and U16 rev binding element (U16RBE) decoys. The functional inhibition of HIV-1 mediated by these nucleolar localizing RNAs implicates nucleolar trafficking or accumulation of HIV transcripts. Investigations centering on HIV-1 regulatory proteins Tat and Rev indicate a necessary translocation step for these proteins within nucleoli for successful HIV replication. This chapter reviews the role of the nucleolus in HIV infection and discusses HIV-specific therapies that manipulate nucleolar localization of HIV regulatory proteins and transcripts. © 2011 Springer Science+Business Media, LLC.