Program Overview > Program Members > Shinji, Harada

Faculty of Life Sciences, Professor
Virology, D.Med.Sci.   Deputy Program director, Program Board member, Research on neutralizing antibodies against HIV

We reported that small changes in the fluidity of the plasma membrane and/or viral envelope would be indispensable for modifying HIV-1 infectivity (1), hypothesizing that fluidity-mediated accumulation of fusion-activated domains was required to form a wide fusion pore large enough for an enveloped viral core to pass through. In fact, the increased or decreased fluidity changes observed after different treatments with the same fluidity modulator, such as glycyrrhizin (2) or fattiviracin FV-8 (3), were parallel with the high or low susceptibility of the treated cells to HIV-1 infection and fusion. These modulators are broad antiviral agents, which are especially effective against enveloped viruses. Furthermore, they were found to reduce the infectivity of virions when the viruses were pretreated (2,3). Notably, this latter finding reminded us of the actions of neutralizing antibodies against viral particles.

To gain further insights into the functions of membrane/envelope fluidity in HIV-1 infection and neutralization, we designed a series of experiments to examine the effects of neutralizing antibodies on the fluidization of the HIV-1 envelope and plasma membrane. We found that these antibodies suppressed the fluidization of the highly ordered lipid bilayer of the viral envelope when they exerted neutralization against the respective virus (4). These studies provide novel insights into the cell biology of retroviral penetration and demonstrate distinct roles for membrane fluidity at early stages of HIV-1 penetration.

1.	Harada, S., Yusa, K., Monde, K., Akaike, T., Maeda, Y., 2005. Influence of membrane fluidity on human immunodeficiency virus type 1 entry. Biochem. Biophys. Res. Commun. 329, 480-486.
2.	Harada, S., 2005. The broad anti-viral agent glycyrrhizin directly modulates the fluidity of plasma membrane and HIV-1 envelope. Biochem. J. 392, 191-199.
3.	Harada, S., Yokomizo, K., Monde, K., Maeda, Y., Yusa, K., 2007. A broad antiviral neutral glycolipid, fattiviracin FV-8, is a membrane fluidity modulator. Cell. Microbiol. 9, 196-203.
4.	Harada, S., Monde, K., Tanaka, Y., Kimura, T., Maeda, Y., Yusa, K., 2008. Neutralizing antibodies decrease the envelope fluidity of HIV-1. Virology 370, 142-150.