HIV-1 virions rendered non-infectious with preservation of conformational and functional integrity of virion surface proteins

Whole inactivated viral particles have been successfully utilized as vaccines for some viruses, but procedures historically used for inactivation can denature virion proteins. Results have been inconsistent, with enhancement of disease rather than protection seen in some instances following vaccination. We used the compound aldrithiol-2 to covalently modify the essential zinc finger motifs in the nucleocapsid protein of HIV-1 virions, thereby inactivating infectivity. The inactivated virus was not detectably infectious in limiting dilution culture (3-4.5 logs inactivation). However, in contrast to virions inactivated with conventional methods such as heat or formalin treatment, viral and host cell derived proteins on virion surfaces retained conformational and functional integrity. Thus, immunoprecipitation of treated virions was comparable to precipitation of matched untreated virus, even using antibodies to conformational determinants on gp120. The MHC Class II molecules on the surface of aldrithiol-2-treated virions produced from MHC Class II positive cells retained the ability to support Class II-dependent, superantigen triggered proliferative responses by resting T lymphocytes. These findings indicate that inactivation via this method results in elimination of infectivity with preservation of conformation and functional integrity of virion surface proteins. Such inactivated virions should be an interesting candidate vaccine antigen and a useful reagent for experimentally probing the postulated involvement of virion surface proteins in HIV-1 pathogenesis.

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