The role of the viral glycoprotein in HIV-1 persistence

The study of the immunological defects which arise from HIV infection has led to a deeper understanding both of the normal immune system and of the mechanisms by which it is damaged in disease. The interactions between viral and host factors during the early stages of HIV infection leads to a post-seroconversion steady state or 'set point' of viral RNA load, which has been shown to be a prognostic marker for subsequent progression rates, further underlining the important role of early immunological responses in the disease process. The changing immune response during the course of infection, together with the changing patterns of antigenicity and tropism leads to a complex series of evolutionary interactions which can be monitored as a series of changes in the properties of the virus over time. Furthermore, significant differences may be seen between the antigenicity of viruses adapted to grow in tissue culture and viruses cultured only briefly in primary cells, and also between the antigenicity of monomeric and oligomeric subunit immunogens. The immunodominant, highly polymorphic and rapidly changing envelope glycoproteins of HIV remains the single biggest target for the design of successful candidate vaccines. The recent crystallisation of one HIV envelope, the proven existence of functionally conserved neutralisation targets and our increasing knowledge of the behaviour of the envelope glycoprotein in vivo offers the possibility that the next generation of vaccine candidates will have a far higher chance of success than has currently been achieved.