Inhibition of CCR5 and CXCR4 prevents HIV infection

Abstract

CCR5 and CXCR4 are chemokine receptors recognize by HIV to enter into the host cell. In this review, we focus on their biology, function and pivotal role in HIV-1 infection, and also, how HIV quasi-species change tropism depending on their expression on the cell surface. We also discuss about the state-of-the-art strategies for targeting CCR5 and CXCR4, with emphasis on novel gene therapies that mimic a natural mutation called CCR5-delta32, enabling innate protection against HIV R5 strains. Trials with gene therapies can knockout both co-receptors and confer protection in vitro without mutants. These techniques include zinc finger nucleases (ZFN), clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRSIRP/Cas9), transcription activator-like effectors nuclease (TALEN), short hairpin RNA (shRNA), and ribozymes.