Areas of Interest
Assembly and Spread of Enveloped Viruses
As obligatory parasites, viruses utilize a large number of host factors and subcellular structures at various stages of their life cycle. Therefore, analyses of virus life cycle promise to increase our knowledge of not only viruses but also cellular machinery with which viral proteins interact.
We are particularly interested in assembly and spread of HIV-1 and influenza A virus, two viral pathogens that have been affecting human health in tremendous ways. Both are enveloped viruses that assemble their progeny at the plasma membrane. Through understanding mechanisms by which host cell structures and components regulate assembly and spread of these viruses, we hope to provide insights into new therapeutic strategies targeting virus-host interactions. Three major areas of research in my laboratory are:
i) Molecular mechanisms that direct viral components to the plasma membrane. Our goal in this area is to fully understand the trafficking of HIV-1 structural protein Gag to the plasma membrane following its translation at ribosomes in the cytoplasm. We are currently focusing on the mechanisms by which acidic phospholipids (e.g., PIP2) and host RNAs regulate this trafficking step, an essential early step in HIV-1 particle assembly.
ii) Mechanisms regulating assembly of viral components and effects of host factors. We seek to elucidate the mechanisms regulating interactions between multiple viral components involved in assembly of influenza A virus particles at the plasma membrane. Our main focus is on a cytoskeleton-mediated antiviral mechanism by which host cells inhibit interactions between viral components in a cell-type-dependent manner.
iii) Relationships between virus assembly at the plasma membrane and subsequent virus spread. In this front, we seek to understand the roles played by a specific subset of host transmembrane proteins incorporated into nascent HIV-1 particles. Ongoing studies are aimed at fully understanding the mechanisms promoting the efficient incorporation of these proteins and the positive and/or negative effects of these virion-incorporated proteins on subsequent infection into new target cells.
Chukkapalli, V., S.J. Oh and A. Ono.* 2010. Opposing mechanisms involving RNA and lipids regulate HIV-1 Gag membrane binding through the highly basic region of the matrix domain. Proc. Natl. Acad. Sci. USA. 107:1600-1605.
Llewellyn, G.N., I.B. Hogue, J.R. Grover, and A. Ono.* 2010. Nucleocapsid promotes localization of HIV-1 Gag to uropods that participate in virological synapses between T cells. PLoS Pathogens 6:e1001167.
Chukkapalli, V. and A. Ono* 2011. Molecular determinants that regulate plasma membrane association of HIV-1 Gag. J.Mol.Biol. 410:512-524. (review)
Hogue, I.B., J.R. Grover, F. Soheilian, K. Nagashima, and A. Ono.* 2011. Gag Induces the Coalescence of Clustered Lipid Rafts and Tetraspanin-Enriched Microdomains at HIV-1 Assembly Sites on the Plasma Membrane. J Virol. 85:9749-9766.
Monde, K., R. Contreras-Galindo, M.H. Kaplan, D.M. Markovitz, and A. Ono.* 2012. HERV-K Gag coassembles with HIV-1 Gag and reduces the release efficiency and infectivity of HIV-1. J Virol. 86: 11194-11208.
Grover, J.R., G.N. Llewellyn, F. Soheilian, K. Nagashima, S.L. Veatch*, and A. Ono.* 2013. Roles Played by Capsid-Dependent Induction of Membrane Curvature and Gag-ESCRT Interactions in Tetherin Recruitment to HIV-1 Assembly Sites. J. Virol. 87: 4650-4664.
Llewellyn, G.N., J.R. Grover, B. Olety, and A. Ono.* 2013. HIV-1 Gag Associates with Specific Uropod-Directed Microdomains in a Manner Dependent on its MA Highly Basic Region. J. Virol. 87: 6441-6454.
Chukkapalli, V.#, J. Inlora#, G. C. Todd, and A. Ono.* 2013. Evidence in support of RNA-mediated inhibition of phosphatidylserine-dependent HIV-1 Gag membrane binding in cells. J. Virol. 87: 7155-7159.
Olety, B. and A. Ono.* 2014. Roles played by acidic lipids in HIV-1 Gag membrane binding. Virus Research 2014 193:108-115. (review)
Inlora, J., D.R. Collins, M.E. Trubin, J.Y. Chung, and A. Ono.* 2014. Membrane binding and subcellular localization of retroviral Gag proteins are differentially regulated by MA interactions with phosphatidylinositol-(4,5)-bisphosphate and RNA. MBio. 5:e02202
Grover, J.R., S.L. Veatch,* and A. Ono.* 2015. Basic motifs target PSGL-1, CD43, and CD44 to plasma membrane sites where HIV-1 assembles. J. Virol. 89:454-467.
Olety, B., S.L. Veatch, and A. Ono.* 2015. Phosphatidylinositol-(4,5)-Bisphosphate Acyl Chains Differentiate Membrane Binding of HIV-1 Gag from That of the Phospholipase Cδ1 Pleckstrin Homology Domain. J. Virol. 89:7861-7873.
Inlora, J., V. Chukkapalli, S. Bedi, and A. Ono.* 2016. Molecular Determinants Directing HIV-1 Gag Assembly to Virus-Containing Compartments in Primary Macrophages. J Virol. 90:8509-8519.
Todd, G.C., A. Duchon, J. Inlora, E.D. Olson, K. Musier-Forsyth, and A. Ono.* 2017. Inhibition of HIV-1 Gag-membrane interactions by specific RNAs. RNA 23: 395-405.
Murakami, T., Kim, J., Li, Y., Green, G.E., Shikanov, A., and A. Ono.* 2018. Secondary lymphoid organ fibroblastic reticular cells mediate trans-infection of HIV-1 via CD44-hyaluronan interactions. Nature Commun. 9: 2436.
Bedi, S.,T. Noda, Y. Kawaoka, and A. Ono.* 2018. A Defect in Influenza A Virus Particle Assembly Specific to Primary Human Macrophages. MBio. 9:e01916
Bedi, S. and A. Ono.* 2019. Friend or Foe: The Role of the Cytoskeleton in Influenza A Virus Assembly. Viruses. 11:E46 (review)
Murakami, T., Carmona, N., and A. Ono.* 2020. Virion-incorporated PSGL-1 and CD43 inhibit both cell-free infection and transinfection of HIV-1 by preventing virus-cell binding. Proc. Natl. Acad. Sci. USA. 117:8055-8063.
* corresponding author(s)
# equal contributions