HIV-INFECTION - THE VIRAL FACTORS

Although many discoveries have led to the development of treatments, A IDS still remains irrevocably a lethal disease. Virus resistance to an tiviral agents is a major hurdle to overcome in the search for an effi cient therapeutic intervention. Viral population turnover dynamics in the host has revealed that some infected latent non-dividing cells bec ome sanctuaries of viral replication. Opposite to productively infecte d cells, that contribute to the replenishment of the viral population, these chronically infected cells are not easily accessible to current treatments. The recent finding that chemokine receptors act as the en igmatic HIV Viral co-receptors for viral entry has opened the way to p ossible new antiviral products. Comprehension of the key mechanisms of viral membrane fusion has now been greatly enhanced by the discovery of CXCR4 and CCR-5 as major factors in viral replication and tropism. Although preliminary results on the specific regions of co-receptors i mplicated in their various functions have been investigated, it remain s uncertain if such regions can be clearly defined. Possible effects o f chemokine receptor use by HIV on signal transduction are also being studied. Following the translocation of the viral core into the cytopl asm, several events are potential targets for antiviral intervention. The active transport of the pre-integration complex to the nucleus is a landmark event in HIV replication. Inhibition of such a phenomenon c ould directly prevent the infection of non-dividing cells (such as mac rophages), and contribute to the elimination of the latently infected ''sanctuary'' cells. The best I known AIDS antiviral therapy remains a gainst reverse transcription. Insights into the role of viral nucleopr otein NCp7 in efficient RT action and infectious particle formation ha ve proposed new, broader multi-target intervention, based on inhibitin g the multifunctional NCp7 protein. Finally, the role of the accessory proteins Vpu and Nef is currently under investigation. The understand ing of the mechanisms behind the effect of these two proteins on viral infectivity, release and budding, specifically through interactions w ith CD4 or with other cellular partners, will give clues to possible d evelopment of stable, attenuated viruses for use as anti-HIV vaccines.