[Frontiers in Bioscience 8, d143-155, January 1, 2003]

RETROVIRAL RECOMBINATION: REVIEW OF GENETIC ANALYSES

Wei-Shau Hu1, Terence Rhodes1,2, Que Dang1,2, and Vinay Pathak1

1 HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA, 2 Department of Microbiology, Immunology, and Cell Biology, School of Medicine, West Virginia University, Morgantown, West Virginia 26506, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The mechanisms of retroviral recombination
3.1. Frequent recombination: the genetic consequences of packaging two viral RNA copies into one viral particle
3.2. Proposed mechanisms of retroviral recombination
3.3. Experimental evidence supporting the recombination models
3.4. Dynamic copy-choice model of retroviral recombination
4. The properties of retroviral recombination
4.1. Recombination rates and the effects of homology on recombination
4.2. Retroviral recombination has high negative interference
4.3.Position and accuracy of recombination events
4.4. Double infection can indirectly affect the occurrence of recombination
5. Recombination in infected hosts
6. Conclusions and implications
7. Acknowledgement
8. References

1. ABSTRACT

Retroviruses package two copies of genomic RNA into one virion. One of the essential steps of replication is reverse transcription, in which the virally encoded enzyme reverse transcriptase (RT) uses the packaged RNA as a template to synthesize viral DNA. Because two copies of RNA are present in one virion, it is possible for RT to switch from one copy of the viral RNA to the other copy during DNA synthesis, thereby generating a recombinant containing some genetic information from each of the RNAs. Recombination occurs at high frequencies during retroviral replication. This frequent recombination has a significant impact on the current human immunodeficiency virus type 1 (HIV-1) epidemic as well as the development of retrovirus-based systems for gene therapy. In this review, the rates, mechanisms, and properties of retroviral recombination are summarized from recent genetic studies. Implications of these studies are also discussed.