BIOLOGY OF LENTIVIRUS SURFACE CARBOHYDRATES

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HIV and the animal lentiviruses are poor inducers of neutralizing antibodies either during infection or in immunized experimental animals. Further, the effectiveness of neutralizing antibodies in protecting against HIV Infection is difficult to evaluate because of lack of data on differences between the affinity of antibodies for the virus and virus for the host cell. Studies on neutralization of the animal lentiviruses show that affinity between antibodies and virus is very low. Morevoer, viruses which are the poorest inducers of, and reactors with, neutralizing antobides are covered with a dense layer of carbohydrates. Our hypothesis is that viral surface carbohydrates are crucial for inducing and reacting with neutralizing antibodies and for binding to cells. Preliminary data already show that neuraminidase has major biological effects on the viruses. Using various substrates of virus, virus-infected cells and deglycosylated virus-infected cells to absorb immune sera; we will determine whether virus surface carbohydrates are the major epitopes in virus neutralization. We will also determine whether the viral carbohydrates are essential for binding of the virus to cells and later penetration of the cells. Finally, we will perform a detailed analysis of the structure of the viral carbohydrates with respect to O- and N-linked glycosylation on two prototype viruses that vary widely in biological properties.