RetrovirusesBiology, Pathogenic Mechanisms and Treatment

Published October 2007 17 lectures
Prof. Robert Gallo
Institute of Human Virology, University of Maryland Baltimore, USA
Summary

Retroviruses are enveloped RNA viruses which replicate through a DNA intermediate, i.e., RNA→DNA→RNAM. The process of DNA synthesis is catalyzed by a special DNA polymerase called reverse transcriptase which is carried by all retroviruses. Once formed the DNA form integrates into the chromosomal DNA of the target cell where it... read moreis known as the provirus. Thus, the cell is permanently infected, and the progeny of that cell also contain proviruses so that the individual animal or human is permanently infected.

Retroviruses are of special interest for two practical reasons: (1) because the process of reverse transcription (RNA→DNA) provided a special tool, namely the synthesis of cDNAs from RNA including the capacity to transcribe mRNA from cells into their corresponding cDNA, that became widely applicable in molecular biology, and (2) because of their capacity to cause serious diseases in animals and humans in an unconventional fashion, usually requiring years from infection to disease rather than days or weeks.

Retroviruses are known to cause cancers, neurological disorders, autoimmunity, and a variety of haematopoietic defects including immune deficiencies in animals and in humans. A detailed understanding of their replication cycle and biology has given rise to the first successful anti-viral therapy in the history of medicine. The future will demand ever more sophisticated understanding of their molecular "tricks" in order to "keep up" with drug resistant variants of retroviruses that emerge with drug treatment and to overcome the inherent major obstacle in the development of successful preventive vaccines against them.

The objective of this series is to provide a comprehensive overview of the types of retroviruses, their basic biology, and pathogenic mechanisms, and the current and future approaches to the treatment of HIV disease, and pathways toward a successful HIV preventive vaccine. Some attempts will be made to fulfill these objectives in a historical perspective.