Retroviral reverse transcriptases

Abstract

Reverse transcription is a critical step in the life cycle of all retroviruses and related retrotransposons. This complex process is performed exclusively by the retroviral reverse transcriptase (RT) enzyme that converts the viral single-stranded RNA into integration-competent double-stranded DNA. Although all RTs have similar catalytic activities, they significantly differ in several aspects of their catalytic properties, their structures and subunit composition. The RT of human immunodeficiency virus type-1 (HIV-1), the virus causing acquired immunodeficiency syndrome (AIDS), is a prime target for the development of antiretroviral drug therapy of HIV-1/AIDS carriers. Therefore, despite the fundamental contributions of other RTs to the understanding of RTs and retrovirology, most recent RT studies are related to HIV-1 RT. In this review we summarize the basic properties of different RTs. These include, among other topics, their structures, enzymatic activities, interactions with both viral and host proteins, RT inhibition and resistance to antiretroviral drugs.

Thymidine Analogue Excision and Discrimination Modulated by Mutational Complexes Including Single Amino Acid Deletions of Asp-67 or Thr-69 in HIV-1 Reverse Transcriptase

“…The human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a heterodimeric enzyme that converts the single-stranded viral genomic RNA into double-stranded DNA, which is integrated into the host genome (1,2). HIV-1 RT is composed of subunits of 560 and 440 residues, designated as p66 and p51, respectively.…”

HIV-Screening Strategies for the Discovery of Novel HIV-Inhibitors

“…Utilization in screening campaigns of RT or PT enzymes that contain drug resistant mutations is a common strategy for identifying next-generation HIV-1 inhibitors against these targets. HIV-1 RT is a multifunctional enzyme involved in several essential activities for viral replication (Sarafianos et al, 2009, Herschhorn & Hiz, 2010. These activities include DNAand RNA-dependent DNA polymerase, ribonuclease H (RNase H), strand transfer and strand displacement activities.…”

Lentiviral Vectors in Immunotherapy

“…Pol encodes enzymatic proteins associated to reverse transcription, that is, the reverse transcriptase (RT), integrase (IN) and protease (PR). RT synthesizes a single cDNA copy from the retrovirus genomic RNA [4]. IN mediates cDNA integration in the host cell chromosome, while PR cleaves Gag and Gag-Pol polyproteins during virion maturation.…”