Molecular Signatures of HIV-1 Envelope Associated with HIV-Associated Neurocognitive Disorders

The HIV-1 envelope gene (env) has been an intense focus of investigation in the search for genetic determinants of viral entry and persistence in the central nervous system (CNS).

Molecular signatures of CNS-derived HIV-1 env reflect the immune characteristics and cellular constraints of the CNS compartment. Although more readily found in those with advanced HIV-1 and HIV-associated neurocognitive disorders (HAND), molecular signatures distinguishing CNS-derived quasispecies can be identified early in HIV-1 infection, in the presence or absence of combination antiretroviral therapy (cART), and are dynamic. Amino acid signatures of CNS-compartmentalization and HAND have been identified across populations. While some significant overlap exists, none are universal. Detailed analyses of CNS-derived HIV-1 env have allowed researchers to identify a number of molecular determinants associated with neuroadaptation. Future investigations using comprehensive cohorts and longitudinal databases have the greatest potential for the identification of robust, validated signatures of HAND in the cART era.