HIV Entry and Its Inhibition by Bifunctional Antiviral Proteins

Alexander Falkenhagen; Sadhna Joshi

doi:10.1016/j.omtn.2018.09.003

HIV Entry and Its Inhibition by Bifunctional Antiviral Proteins

Mol Ther Nucleic Acids. 2018 Dec 7:13:347-364. doi: 10.1016/j.omtn.2018.09.003. Epub 2018 Sep 11.

Authors

Alexander Falkenhagen¹, Sadhna Joshi²

Affiliations

¹ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E2, Canada.
² Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E2, Canada. Electronic address: sadhna.joshi.sukhwal@utoronto.ca.

Abstract

HIV entry is a highly specific and time-sensitive process that can be divided into receptor binding, coreceptor binding, and membrane fusion. Bifunctional antiviral proteins (bAVPs) exploit the multi-step nature of the HIV entry process by binding to two different extracellular targets. They are generated by expressing a fusion protein containing two entry inhibitors with a flexible linker. The resulting fusion proteins exhibit exceptional neutralization potency and broad cross-clade inhibition. In this review, we summarize the HIV entry process and provide an overview of the design, antiviral potency, and methods of delivery of bAVPs. Additionally, we discuss the advantages and limitations of bAVPs for HIV prevention and treatment.

Keywords: HIV; antiviral proteins; bifunctional; entry; entry inhibitors; gene therapy.

Publication types

Review