Neutralization epitopes on HIV pseudotyped with HTLV-I

Abstract

During the last decade, research efforts have been aimed at development of an HIV vaccine. Until now it has not been possible to identify conserved epitopes on the envelope structure of HIV, which might be targets for neutralizing antibodies. However, it is clear that the conformation of gp120 is important for the development of broadly neutralizing antibodies, and that glycan structures of gp120 are of importance in this context. HIV-infected patients are often co-infected with other viruses, and one mechanism for expanding the cellular tropism of HIV in vitro is through formation of phenotypically mixed particles (pseudotypes) with HTLV-I. Previously, pseudotypes were found to allow penetration of HIV particles into CD4-negative cells, which are otherwise nonsusceptible to HIV infection. In the search for epitopes that might be the target for an HIV vaccine, the pseudotype phenomenon should be taken into account. An HIV-neutralizing antibody, induced by a vaccine, should also be able to neutralize potential pseudotypes. The in vitro infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum, but failed to be significantly inhibited with antibodies directed at HIV. These findings suggest that pseudotypes may represent a way to escape neutralization by the immune system in vivo. Previous reports have indicated that carbohydrate structures may be conserved neutralization epitopes on retroviruses. Lectins and monoclonal antibodies directed to carbohydrate structures were found to block HIV/HTLV-I pseudotype infection in CD4-negative cells. Therefore, although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes. Taken together, these results indicate that carbohydrate structures might induce protective antibodies, in spite of HIV envelope protein variability and the possibility of pseudotype production, which is why the results may be used in the search of an HIV vaccine or immune-stimulating agents.