Jaisri Lingappa’s lab studies how viruses hijack host proteins to promote assembly of human immunodeficiency virus type 1 (HIV-1) and other viruses, using biochemical and cell biological approaches. Our group has demonstrated that, in cells, the assembly of immature HIV-1 capsids occurs through a pathway of assembly intermediates, and is facilitated by the catalytic activity of the host enzymes ABCE1 and DDX6. To form assembly intermediates (also called “assembly machines”), HIV-1 co-opts sites of RNA metabolism called RNA granules. Our most recent studies suggest that:
- HIV-1 genomic RNA is largely sequestered within RNA granules in infected cells.
- The HIV-1 capsid protein Gag initiates genome packaging by entering RNA granules containing HIV-1 genomic RNA.
- A highly conserved viral-host interaction directs Gag to RNA granules containing HIV-1 genomic RNA.
- Mutations in Gag that arise in vivo alter the ability of Gag to enter RNA granules and progress through the assembly pathway, thereby altering the kinetics of virus production.
More Background on Our Research
About Our Current Research Questions
Recent Lingappa Lab Publications
Michon, M, Müller-Schiffmann, A, Lingappa, AF, Yu, SF, Du, L, Deiter, F, Broce, S, Mallesh, S, Crabtree, J, Lingappa, UF, Macieik, A, Müller, L, Ostermann, PN, Andrée, M, Adams, O, Schaal, H, Hogan, RJ, Tripp, RA, Appaiah, U, Anand, SK, Campi, TW, Ford, MJ, Reed, JC, Lin, J, Akintunde, O, Copeland, K, Nichols, C, Petrouski, E, Moreira, AR, Jiang, IT, DeYarman, N, Brown, I, Lau, S, Segal, I, Goldsmith, D, Hong, S, Asundi, V, Briggs, EM, Phyo, NS, Froehlich, M, Onisko, B, Matlack, K, Dey, D, Lingappa, JR, Prasad, MD, Kitaygorodskyy, A, Solas, D, Boushey, H, Greenland, J, Pillai, S, Lo, MK, Montgomery, JM, Spiropoulou, CF, Korth, C, Selvarajah, S, Paulvannan, K, Lingappa, VR. A Pan-Respiratory Antiviral Chemotype Targeting a Host Multi-Protein Complex. bioRxiv. 2023; :. doi: 10.1101/2021.01.17.426875. PubMed PMID:34931190 PubMed Central PMC8687465.
Lingappa, JR, Lingappa, VR, Reed, JC. Addressing Antiretroviral Drug Resistance with Host-Targeting Drugs-First Steps towards Developing a Host-Targeting HIV-1 Assembly Inhibitor. Viruses. 2021;13 (3):. doi: 10.3390/v13030451. PubMed PMID:33802145 PubMed Central PMC8001593.
Reed, JC, Solas, D, Kitaygorodskyy, A, Freeman, B, Ressler, DTB, Phuong, DJ, Swain, JV, Matlack, K, Hurt, CR, Lingappa, VR, Lingappa, JR. Identification of an Antiretroviral Small Molecule That Appears To Be a Host-Targeting Inhibitor of HIV-1 Assembly. J Virol. 2021;95 (3):. doi: 10.1128/JVI.00883-20. PubMed PMID:33148797 PubMed Central PMC7925099.
Barajas, BC, Tanaka, M, Robinson, BA, Phuong, DJ, Chutiraka, K, Reed, JC, Lingappa, JR. Identifying the assembly intermediate in which Gag first associates with unspliced HIV-1 RNA suggests a novel model for HIV-1 RNA packaging. PLoS Pathog. 2018;14 (4):e1006977. doi: 10.1371/journal.ppat.1006977. PubMed PMID:29664940 PubMed Central PMC5940231.
Reed, JC, Westergreen, N, Barajas, BC, Ressler, DTB, Phuong, DJ, Swain, JV, Lingappa, VR, Lingappa, JR. Formation of RNA Granule-Derived Capsid Assembly Intermediates Appears To Be Conserved between Human Immunodeficiency Virus Type 1 and the Nonprimate Lentivirus Feline Immunodeficiency Virus. J Virol. 2018;92 (9):. doi: 10.1128/JVI.01761-17. PubMed PMID:29467316 PubMed Central PMC5899207.
Sette, P, O'Connor, SK, Yerramilli, VS, Dussupt, V, Nagashima, K, Chutiraka, K, Lingappa, J, Scarlata, S, Bouamr, F. HIV-1 Nucleocapsid Mimics the Membrane Adaptor Syntenin PDZ to Gain Access to ESCRTs and Promote Virus Budding. Cell Host Microbe. 2016;19 (3):336-48. doi: 10.1016/j.chom.2016.02.004. PubMed PMID:26962944 PubMed Central PMC4804359.