DESIGN AND CONSTRUCTION OF NON-INFECTIOUS HUMAN RETROVIRUS MUTANTS WITH A LACK OF GENOMIC RNA

摘要

The present invention defines a biological role for the following sequence of amino acids that is found in the nucleocapsid domain of the gag precursor polyproteins of all replication-competent retroviruses: -Cys-X-X-Cys-X-X-X-X-His-X-X-X-X-Cys-, wherein X represents variable amino acids. The invariant residues constitute part of a vital protein structure, at least one of which are found in all retroviruses and which are involved in the selection and packaging of genomic viral RNA into infectious virus particles. Disruption of this structure leads to the formation of virus-like particles which appear to be structurally normal, but which do not contain the normal complement of viral RNA. Therefore, their infectivity is drastically reduced or completely eliminated. The infectivity of any retrovirus, including human retroviruses, and more particularly human immunodeficiency virus (HIV), can be drastically reduced or completely eliminated by generating mutants that lack some or all of the invariant residues required to form the structure. In addition, any means of disrupting the functions of this array will in turn disrupt the viral life cycle. Thus, with the knowledge provided by this invention, chemotherapeutic reagents aimed toward this array may be devised.