Receptor for Sialic Acids
Lectins that recognize sialic acids, especially members of the Siglec family (sialic acid-recognizing Ig-superfamily lectins) turn out to be important players in our propensity for disease. As we previously discussed, humans lack a hydroxylase gene necessary for the hydroxylation of Neu5Ac to Neur5Gc which is found in chimps who possess the enzyme. Chimps' immune systems seem to confer protection from acquiring the simian version of AIDS, cirrhosis, and other diseases which humans acquire when they are infected with the human versions of the HIV virus, hepatitis B or C, or other viruses. These diseases and others associated with overactive T cells (rheumatoid arthritis, asthma, type-I diabetes) are not common in chimps. It turns out that there is a link between the type of sialic acid and the expression of siglecs that influences the difference on our disease propensity. Varki et al. have shown that chimps and gorillas show much higher levels of expression of Siglecs on T cells, which are critical regulatory and effector cells in the immune system. When siglecs on T cells are activated, T-cell responses are down regulated. Although HIV virus ultimately kills T helper cells, the virus initially activates them on infection, leading to their proliferation and production of a larger number of cells for the virus to infect.
Influenza virus (which has caused some of the greatest pandemics in world history) also binds to sialic acid on host cells, through a viral binding protein called hemagglutinin. On binding, conformational changes activate a neuraminidase activity of another viral protein, allowing cleavage of the sialic acid glycosidic bond, and subsequent entry of the virus into the cell.