The plasma membrane is not a homogenous sea of lipid; it rather consists of various microdomains with specific sets of protein and lipid components.  Microdomains such as lipid rafts are implicated in multiple cellular functions including signaling and trafficking. Notably, assembly of HIV-1 and influenza A virus particles occurs at the plasma membrane region enriched with these microdomains.  These microdomains play important role(s) in both virus assembly and particle infectivity.  Furthermore, these microdomains are implicated in virion incorporation of host cellular membrane proteins that restrict or facilitate spread of nascent virus particles. We aim to fully understand the relationships between local plasma membrane properties and enveloped virus assembly. Using microscopy techniques including fluorescence resonance energy transfer, correlative light and electron microscopy, and super-resolution localization microscopy*, we have shown that HIV-1 Gag multimerization at the plasma membrane alters microdomain organization and coalesces different types of microdomains. We also revealed that membrane curvature induced by Gag multimerization promotes recruitment of tetherin, a host membrane protein with an antiviral function, to the site of virus assembly. Our current focus is on host membrane properties involved in efficient incorporation of uropod proteins [see (iii)] into nascent virus particles. 

For formation of influenza A virus particles, 3 transmembrane proteins (HA, NA, and M2) and 2 cytoplasmic components (M1 and vRNPs) need to come together at the plasma membrane. While some of molecular interfaces have been identified, how the entire process is orchestrated remains poorly understood. We seek to elucidate the mechanisms regulating interactions between different viral components and host factors involved in this process. We found that in human monocyte-derived macrophages, virus particle formation is blocked due to a cell-specific and actin-dependent restriction of HA-M2 association at the plasma membrane. Our current priorities on this front are to identify the host factor involved in this inhibitory activity and to determine how actin cytoskeleton affects the behavior of each viral component necessary for virus particle formation.

*in collaboration with Dr. Sarah Veatch's lab in Dept. Biophysics

[Publications in this area]

Hogue, I.B., A. Hoppe, and A. Ono. 2009. J Virol. 83:7322-7336.

Hogue, I.B., et al. 2011. J Virol. 85:9749-9766.

Monde, K., et al. 2012. J Virol.  86: 11194-11208.

Grover, J.R., et al. 2013. J. Virol. 87: 4650-4664.

Llewellyn, G.N., et al. 2013. J. Virol. 87: 6441-6454.

Grover, J.R., S.L. Veatch, and A. Ono. 2015. J. Virol. 89:454-467.

Bedi, S., et al. 2018. MBio 9:e01916.

Bedi, S., et al. 2022. J. Virol. 96:e0071622.