Baculovirus Reveals a New pH-dependent Direct Cell-fusion Pathway For Cell Entry and Transgene Delivery

Abstract

Evaluation of: Dong S, Wang M, Qiu Z et al.: AcMNPV efficiently infects Sf9 cells and transduces mammalian cells via direct fusion with the plasma membrane at low pH. J. Virol. 84(10), 5351–5359 (2010). The article evaluated unravels the existence of an alternative infection pathway of baculoviruses, such as Autographa californica multiple nuclear polyhedrosis virus, for infection of insect cells by altering pH conditions. The authors have demonstrated that lowering the pH within an insect cell can induce baculovirus cell entry through an alternative direct cell membrane fusion pathway independent of the normal endocytosis pathway. They explain that this mode of cell entry and the corridor to the nucleus is dependent on myosin-like proteins and not on microtubules. The article also reports, for the first time, that baculovirus can also efficiently transduce mammalian cells using a direct fusion pathway induced by a short pH trigger, which can be further enhanced by completely blocking the probable endocytosis pathway. These findings by Dong et al. provide us with a further step in understanding the different routes by which baculovirus can enter insect and mammalian cells. In fact, this study gives us an insight to the development of a novel pH-dependent baculovirus-mediated therapeutic strategy for efficient transgene delivery to mammalian cells and also for an advanced insect cell-based protein production system.