Role of Nonmuscle Myosin II in Virus-Cell Fusion

Abstract

Membrane fusion is the process whereby two separate lipid bilayers merge to become one. Despite substantial progress, an integrated concept for protein–mediated membrane fusion (cellular and viral) is not yet available, and many open questions yet to be answered. Membrane fusion, the merging/intermixing of two lipid bilayers, is quite a well known process involved in a number of physiological functions e.g. fertilization, cell division, myoblast differentiation, transport of impermeant molecules into the cell (endocytosis) and out of the cell (exocytosis). Among all the cases of membrane fusion, viral entry through membrane fusion gains the special attention as viruses’ e.g. parainfluenza virus (PIV), human immunodeficiency virus (HIV), simian immunodeficiency virus (SIV), murine leukemia virus (MLV), herpes simplex virus (HSV), measles virus (MV) etc fuse directly with plasma membrane to enter inside the host cells. These viruses are the etiological agents of many biologically important diseases of man and other animals. The involvement of membrane fusion in all these events makes ‘fusion’ a sizzling issue always and force the scientists to go into its finer details. Virus-cell surface receptor interactions can elicit two types of signals; conformational changes of viral particles, and concomitant intracellular signals triggering specific cellular reactions.1 In this direction, Wang et. al. have shown evidence that cellular signal transduction pathways and associated protein kinases could be responsible in modulating retrovirus-induced cell-cell fusion.2 However, little is known about the virus-induced host cell intracellular signaling in terms of maintaining the actomyosin complex that influences the membrane fusion. Viruses in the paramyxoviridae family and others like HIV (Human immunodeficiency virus), bind to the surface proteins of the host cell and fuse with the plasma membrane to release the nucleoprotein in the cytosol directly to reach the site of their replication. If we talk about membrane fusion in terms of thermodynamics, it is energetically a non-spontaneous process and there is a very high kinetic barrier, so the process needs the catalytic help of proteins (fusion glycoproteins of all viruses and fusogens of all other kind) for using the free energy, liberated during the conformational change of the membrane proteins to draw each other together3(Fig. 1). Moreover, as membrane fusion is the critical step in the course of enveloped animal virus infection, it is logical to think of its regulation by host cell signaling. Keeping this proposition in mind we have studied a precise effect of membrane fusion on actomyosin signaling in the course of viral infection, taking Sendai virus (Z strain) as the model.Research was conducted under the supervision of Prof. S S Jana of Biological Chemistry division under the SBS [School of Biological Sciences]The research was carried out under CSIR, DBT & DST gran