Jaisri Lingappa's Lab

Overview

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

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.

Tanaka, M, Robinson, BA, Chutiraka, K, Geary, CD, Reed, JC, Lingappa, JR. Mutations of Conserved Residues in the Major Homology Region Arrest Assembling HIV-1 Gag as a Membrane-Targeted Intermediate Containing Genomic RNA and Cellular Proteins. J. Virol. 2016;90 (4):1944-63. doi: 10.1128/JVI.02698-15. PubMed PMID:26656702 PubMed Central PMC4734008.

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.

Robinson, BA, Reed, JC, Geary, CD, Swain, JV, Lingappa, JR. A temporospatial map that defines specific steps at which critical surfaces in the Gag MA and CA domains act during immature HIV-1 capsid assembly in cells. J. Virol. 2014;88 (10):5718-41. doi: 10.1128/JVI.03609-13. PubMed PMID:24623418 PubMed Central PMC4019110.

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