Mechanisms contributing to the neutralization of HIV-1

The phenomenon of virus neutralization is a function of three variables: the antibody (Ab), the virus and the target cell. Variation in any one of these parameters may drastically affect the results of assays for neutralization. In focusing on the virus as a variable in assays for the neutralization of HIV-1, it has been shown that the range of sensitivity of primary HIV-1 isolates is quite large. This may be due to the structure and biology of the virus particle, its density of envelope proteins, its ability to retain or shed these proteins, and its phenotype, determining the type of cells it will infect. The Ab used for neutralization also contributes to the efficiency of neutralization. Thus, the 'match' between the specificity of the Ab and the structure and availability of the epitope on the virus will affect the interaction and contribute to the resultant reduction in virus infectivity. Similarly, the strength of interaction between the virus and the neutralizing Ab, dependent on the affinity of the Ab for the virus epitope, will also be a determining factor. However, other factors contribute to the neutralization sensitivity of primary isolates of HIV-1. One factor that has been almost completely overlooked in the recent literature is the role that the target cell plays in revealing reduced virus infectivity. The facility and mechanism through which different cell types bind a virion and are infected by it will contribute profoundly to the efficiency with which Ab-mediated neutralization can be detected. These factors are discussed below with particular reference to interpreting (and re-interpreting) the current literature on HIV-1 neutralization.