Virongy Biosciences develops cutting-edge technologies in virology and viral vectors to accelerate scientific discovery, clinical diagnostics, and disease treatment.

Virongy's Key Technologies

Model of HIV exploitation of actin dynamics to overcome the cortical actin barrier. Cortical actin (green staining, F-actin) in blood CD4 T cells remains relatively static in the absence of chemotactic signaling. Binding of viral envelope protein gp120 to CXCR4/CCR5 triggers a transient course of actin polymerization and depolymerization, through the activation of the cofilin/Arp2/3 pathways, to facilitate viral entry and post-entry nuclear migration.
Infectin is a proprietary technology developed at Virongy and based on the scientific theory that cortical actin is a natural barrier for viral entry and intracellular migration towards the cytosol and the nucleus (Yoder et al., 2008). Cortical actin is a dense meshwork of actin filaments (F-actin) underneath the plasma membrane. It provides mechanical support to cells and is a major driving force for cell motility.

Hybrid alpha-pseudoviruses are a newly developed pseudovirus platform for rapidly screening viral entry inhibitors. They consist of a virus-like particle (VLP) that encapsulates an alphavirus-derived RNA genome for rapid report expression (luciferase or GFP) in target cells (Hetrick et al., 2022).  Ha-CoV-2 represents a major technology advancement in the development of SARS-CoV-2 pseudoviruses, and serves as platforms for rapid and robust quantification of neutralizing antibodies, viral mutants, and antiviral drugs (Dabbagh et al., 2021; He et al., 2021).

Quantification of anti-HIV neutralizing antibody B12 with Rev-A3R5-GFP reporter cells

The HIV Rev-dependent reporter cells licensed and commercialized by Virongy represent a major advancement in the development of HIV indicator cells (Wu et al., 2007). This new reporter system differs dramatically from the common LTR-based reporter cells, which rely solely on the HIV promoter, the long terminal repeat (LTR), to drive reporter expression. 

Endo, M., Ohashi, K., and Mizuno, K. (2007). LIM kinase and slingshot are critical for neurite extension. J Biol Chem 282, 13692-13702.

Foletta, V.C., Moussi, N., Sarmiere, P.D., Bamburg, J.R., and Bernard, O. (2004). LIM kinase 1, a key regulator of actin dynamics, is widely expressed in embryonic and adult tissues. Exp Cell Res 294, 392-405.

Guo J, Wang W, Yu D, Wu Y. Spinoculation triggers dynamic actin and cofilin activity facilitating HIV-1 infection of transformed and resting CD4 T cells. J Virol. 2011; 85(19):9824-33. PubMed PMID: 21795326.

Liu, G., Xiang, Y., Guo, C., Pei, Y., Wang, Y., and Kitazato, K. (2014). Cofilin-1 is involved in regulation of actin reorganization during influenza A virus assembly and budding. Biochem Biophys Res Commun 453, 821-825.

Manetti, F. (2012). Recent Findings Confirm LIM Domain Kinases as Emerging Target Candidates for Cancer Therapy. Curr Cancer Drug Targets 12, 543-560.

Nishimura, Y., Yoshioka, K., Bernard, O., Bereczky, B., and Itoh, K. (2006). A role of LIM kinase 1/cofilin pathway in regulating endocytic trafficking of EGF receptor in human breast cancer cells. Histochem Cell Biol 126, 627-638.

Siekevitz M, Josephs SF, Dukovich M, Peffer N, Wong-Staal F, Greene WC. Activation of the HIV-1 LTR by T cell mitogens and the transactivator protein of HTLV-I. Science. 1987; 238:1575–1578.

Sweet MJ, Hume DA. RAW264 macrophages stably transfected with an HIV-1 LTR reporter gene provide a sensitive bioassay for analysis of signalling pathways in macrophages stimulated with lipopolysaccharide, TNF-alpha or taxol. J Inflamm. 1995; 45:126 –135.

Sigal A, Kim JT, Balazs AB, Dekel E, Mayo A, Milo R, et al. Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy. Nature. 2011; 477(7362):95-8. PubMed PMID: 21849975.

Spear M, Guo J, Turner A, Yu D, Wang W, Meltzer B, et al. HIV-1 triggers WAVE2 phosphorylation in primary CD4 T cells and macrophages, mediating Arp2/3-dependent nuclear migration. J Biol Chem. 2014; 289(10):6949-59. PubMed PMID: 24415754; PubMed Central PMCID: PMC3945356.

Sloan RD, Kuhl BD, Donahue DA, Roland A, Bar-Magen T, Wainberg MA. Transcription of preintegrated HIV-1 cDNA modulates cell surface expression of major histocompatibility complex class I via Nef. J Virol. 2011; 85(6):2828-36. PubMed PMID: 21209113.

Shuck-Lee D, Chang H, Sloan EA, Hammarskjold ML, Rekosh D. Single-nucleotide changes in the HIV Rev-response element mediate resistance to com-pounds that inhibit Rev function. J Virol. 2011; 85(8):3940-9. PubMed PMID: 21289114.

Vorster, P.J., Guo, J., Yoder, A., Wang, W., Zheng, Y., Xu, X., Yu, D., Spear, M., and Wu, Y. (2011). LIM kinase 1 modulates cortical actin and CXCR4 cycling and is activated by HIV-1 to initiate viral infection. J Biol Chem 286, 12554-12564.

Wu Y, Beddall MH, Marsh JW. Rev-dependent indicator T cell line. Current HIV Research. 2007; 5:395-403.

Yang, N., Higuchi, O., Ohashi, K., Nagata, K., Wada, A., Kangawa, K., Nishida, E., and Mizuno, K. (1998). Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Nature 393, 809-812.

Yi, F., Guo, J., Dabbagh, D., Spear, M., He, S., Kehn-Hall, K., Fontenot, J., Yin, Y., Bibian, M., Park, C.M., et al. (2017). Discovery of Novel Small Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol. 91:e02418-16.

Yoshioka, K., Foletta, V., Bernard, O., and Itoh, K. (2003). A role for LIM kinase in cancer invasion. Proc Natl Acad Sci U S A 100, 7247-7252.

Yu D, Wang W, Yoder A, Spear M, Wu Y. The HIV envelope but not VSV glycoprotein is capable of mediating HIV latent infection of resting CD4 T cells. PLoS Pathog. 2009; 5(10):e1000633. PubMed PMID: 19851458.

Yoder A, Yu D, Dong L, Iyer SR, Xu X, Kelly J, et al. HIV envelope-CXCR4 signaling activates cofilin to overcome cortical actin restriction in resting CD4 T cells. Cell. 2008; 134(5):782-92. PubMed PMID: 18775311.