THE NUCLEOCAPSID OF HIV-1 - A PARADIGM FO R RESEARCH AND MEDICAL APPLICATIONS

Retroviruses, composed of the oncoviruses, lentiviruses and spumavirus es, are small animal viruses that can cause various forms of cancer, i mmunodeficiency and degenerative diseases of the central nervous syste m. The viral particle is about 110-130 mm in diameter and is formed of an inner core surrounded by an outer envelope which is a lipid bilaye r of cellular origin containing the viral glycoproteins. The inner cor e can be subdivided into an outer shell of capsid protein molecules an d the interior nucleocapsid where the dimeric RNA genome is in tight a ssociation with a large number of nucleocapsid protein molecules. The viral nucleocapsid also contains few molecules of the viral enzymes re verse transcriptase, integrase, and protease as well as cellular RNAs. In this brief review we have summarized some of the properties and fu nctions of the nucleocapsid of HIV-1 which appears to be a simple and specialized nucleoprotein structure. The nucleocapsid of HIV-1, and of retroviruses in general, is a highly attractive and simple model sinc e it is formed of only one major structural protein, the NC protein, t he viral enzymes and one major RNA, the viral genome, and since it ach ieves basic functions such as the extracellular transport and dissemin ation of the genome, and the synthesis of the infectious proviral DNA in the infected cell. Recent data on the structure of the nucleocapsid protein of HIV-1 and of its functions during virus replication indica te that the nucleocapsid protein is an integral part of the reverse tr anscription machinery. Moreover, the nucleocapsid protein has potent n ucleic acid annealing and strand transfer activities which may well pr omote the high rate of recombination during proviral DNA synthesis, an d therefore the high genetic variability of HIV-1, and of retroviruses in general. These recent findings on the nucleocapsid protein of HIV- 1 should have important applications in the development of anti-HIV th erapies.