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Lingappa, JR, Reed, JC, Tanaka, M, Chutiraka, K, Robinson, BA. How HIV-1 Gag assembles in cells: Putting together pieces of the puzzle. Virus Res. 2014;193 :89-107. doi: 10.1016/j.virusres.2014.07.001. PubMed PMID:25066606 PubMed Central PMC4351045.
This review serves as an introduction to the field for newcomers, but also provides a useful summary to those more familiar with HIV-1 assembly. In it, we describe how different experimental approaches have been used to study assembly of the HIV-1 immature capsid – including analysis of mutations, structural biology, assembly of recombinant Gag, assembly in cell-free systems, imaging, biochemical approaches, and siRNA knockdowns. This review also highlights unanswered questions in the HIV-1 assembly field.
Lingappa, UF, Wu, X, Macieik, A, Yu, SF, Atuegbu, A, Corpuz, M, Francis, J, Nichols, C, Calayag, A, Shi, H, Ellison, JA, Harrell, EK, Asundi, V, Lingappa, JR, Prasad, MD, Lipkin, WI, Dey, D, Hurt, CR, Lingappa, VR, Hansen, WJ, Rupprecht, CE. Host-rabies virus protein-protein interactions as druggable antiviral targets. Proc Natl Acad Sci U S A. 2013;110 (10):E861-8. doi: 10.1073/pnas.1210198110. PubMed PMID:23404707 PubMed Central PMC3593902.
Rabies is almost always fatal and causes a significant number of deaths in developing countries; yet, antiviral drugs for treating the disease are completely lacking. In this paper, Prosetta Biosciences used an assembly pathway screen to identify a small molecule that inhibits rabies capsid assembly. This drug-like compound binds to complexes containing ABCE1, a cellular enzyme that Jaisri Lingappa’s lab has implicated in facilitating HIV-1 capsid assembly. Authors on this paper include investigators at Prosetta Biosciences, the Centers for Disease Control (CDC), and Jaisri Lingappa’s lab at UW.
“Cell Leading Edge Select” commentary on this paper, entitled Targeting the Host-Virus Machinery
Learn more about the rabies drug screen used in this paper from an article by science writer Carl Zimmer in the blog Phenomena by National Geographic, and in a SciBx article.