Expression and characterization of recombinant capsid protein from HIV and its mutants: towards inhibition of virus assembly

Human immunodeficiency virus infection has been a threat to the world for the last thirty years. It causes a condition called acquired immunodeficiency syndrome leading to complete collapse of immune system and death if not treated. There are many anti-HIV drugs that are part of the combined antiretroviral treatment but they only slow down the progress of the infection. Although the success of all the 31 antiviral agents is remarkable, the cure is not efficient enough. The research of potencial new HIV drugs is now focusing on new targets of viral inhibition. The capsid protein is a potential target of virion assembly and maturation inhibitors due to its multimerization features. The N-terminal domains of six capsid proteins create hexamers. These are connected to each other by dimers of the C-terminal domains according to X-ray and NMR studies. There are inhibitors that bind to the C-terminal domain, alter its conformation and weaken the protein-protein interaction of the dimer. Protein calorimetry is a method that could detect and quantify protein-protein interactions and thus capsid protein dimerization and its inhibition. We expressed and purified recombinant wild-type capsid protein and its C-terminal domain that both dimerize in solution and crystals. Their dimerization constant was determined by..