Virus assembly as a target for antiretroviral therapy

The process of HIV assembly is controlled mainly by the viral Gag proteins and represents an attractive target for new antiviral drugs that will complement vaccine development efforts and currently available therapies. In principle, inhibitors may interfere with any of the steps of the virus assembly pathway, including precursor Gag (PrGag) myristoylation, protein trafficking to the cell surface, envelope (Env) protein incorporation, viral RNA (vRNA encapsidation), triggering of virus assembly, immature particle assembly, budding, release, PrGag processing, and mature virus core morphogenesis. Efforts to interfere with these assembly steps will be reviewed. These include investigations designed to interfere with functions of the major HIV-1 Gag proteins, matrix (MA), capsid (CA), nucleocapsid (NC), and p6. Research has achieved proof-of-principle results for inhibitors of several HIV-1 assembly steps, and characterization of these and new classes of HIV assembly inhibitors will yield novel insights relevant to both the basic biology of HIV and to the development of new therapeutics for the treatment of AIDS.