Reverse Transcription of Retroviruses and LTR Retrotransposons

The conversion, well over a billion years ago, of the RNA world into the modern configuration, in which genetic information is maintained primarily in DNA, required reverse transcriptases (RTs), enzymes that were able to copy genetic information from RNA into DNA, a process called reverse transcription. With minor (but important) exceptions, for example telomerases, normal cellular processes no longer require reverse transcription, which is now primarily employed in the replication of hepadnaviruses, retroviruses, and retrotransposons. This chapter will cover the process of reverse transcription, and the RTs that are involved in the replication of retroviruses and the related long terminal repeat (LTR) retrotransposons, which have lifestyles that are similar to a retrovirus that has either lost, or never acquired, the ability to be transmitted horizontally from one cell to another. The RTs of, and reverse transcription by, non-LTR retrotransposons will be considered in the chapters that describe these elements (49–55). A substantial fraction of the work that has been done on reverse transcription and RT has focused on human immunodeficiency virus type 1 (HIV-1); this is entirely appropriate given the extent of the HIV epidemic and the fact that HIV-1 RT is the target of two important classes of anti-HIV drugs. Thus, a substantial portion of this review will describe data and insights obtained in experiments that were done with HIV-1 and HIV-1 RT. However, there are some important differences in the RTs, and the process of reverse transcription, among the different retroviruses and LTR retrotransposons; these differences will also be considered, at least briefly. The literature on RT and reverse transcription is both vast and complex. Any review, including this one, can present no more than a superficial overview of what is known. Much that is important has been omitted, some intentionally, some inadvertently; for these omissions, the author apologizes. For those who are interested, a number of helpful reviews have already been published, most of which are focused on retroviral RTs (1 , 2 , 3 , 4).