Functional Contributions of Carbohydrate on AIDS Virus Glycoprotein

Envelope glycoprotein spikes on the surface of the human immunodeficiency virus (HIV) are used by the virus to bind to cellular receptors to gain entry into target cells. As such, the envelope spikes are the targets of antibodies that can neutralize viral infectivity. Fifty percent or more of the mass of the viral-encoded surface glycoprotein of HIV, and of its close monkey relative simian immunodeficiency virus (SIV), is actually carbohydrate; it is one of the most heavily glycosylated proteins that can be found in mammals. It has been clearly demonstrated that one of the functions of this carbohydrate is to shield viral epitopes that would otherwise be the direct target of antibodies that could neutralize viral infection. In addition, it is now generally accepted that the carbohydrate on the viral envelope glycoprotein is recognized by multiple cellular lectins of the host lymphoreticular system, and these interactions play a role in the dissemination of virus within the host as well as the release of modulatory cytokines. Our work recently demonstrated fundamental differences in the composition of the carbohydrate on HIV type 1, the cause of the AIDS pandemic, versus the SIV in the sooty mangabey monkey, a natural host that does not develop disease from its infection. We now speculate that this fundamental difference in carbohydrate composition reflects evolutionary pressures on both virus and host. Furthermore, carbohydrate composition on the virus and genetic differences in carbohydrate-sensing proteins of the host could be critically important for the generalized lymphoid activation that characterizes the acquired immunodeficiency syndrome (AIDS).