Cellular virology

Viruses cannot multiply without infecting cells. At each round of infection they must fall apart, deliver their genome to the proper site of replication and transcription and then rebuild infectious particles from scratch. As they are relatively ‘simple’ parasites, they require many host cell functions for the various steps of their life cycle. These include the host cell translation machinery, cellular translocation and sorting machinery to target their glycoproteins to their proper cellular destination. As viruses also lack a lipid-synthesizing machinery, they need host membranes to acquire their lipid envelope. Finally, with the exception of poxviruses, DNA viruses require the cellular nucleus for replication. Although viruses strictly depend on cells, they have evolved the ability to use their host in the most effective ways. They use cellular cues to go through ‘programmed’ disassembly steps, with the aim of delivering their genome precisely at the right site of replication (Smith and Helenius, 2004). They subsequently assemble into stable structures within these same cells, obviously avoiding the disassembly cues previously used to allow the particle to fall apart. Cells respond to virus infection by inducing signalling events that favour cellular defence, often leading to cell death. Viruses have not only evolved strategies to prevent cellular apoptosis, but also to use cellular defence reactions to their benefit (Wurzer et al ., 2003). To travel faster through the cellular cytoplasm, they manipulate the cytoskeleton and cellular signal transduction pathways (Suomalainen et al ., 2001). They induce the proliferation of specific cellular membranes to increase surface areas and provide platforms for replication/assembly (reviewed in Salonen et al ., 2005). Considering that most viruses consist of no more than 5–10 proteins, their impact on cells is really quite dramatic and fascinating at the same time. Because various steps of viral life cycles mimic cellular processes, viruses have been and are being used as tools to study cellular processes. The advantage of viruses is that they highlight or induce certain cellular processes that are hard to study otherwise. The GFP-tagged version of the G glycoprotein of vesicular stomatitis virus, in particular its temperature sensitive Ts045 variant, has been used extensively to study transport from the ER to the Golgi complex, also in real time (Presley et al ., 1997; Scales et al ., 1997). The initial finding that the HA protein of influenza virus was insoluble in triton-100 in the cold (Skibbens et al ., 1989) opened up a whole field of research on rafts (Simons and Ikonen, 1997). The G protein of VSV and the HA of influenza, that are targeted to the basolateral and apical plasma membrane, respectively (Rodriguez-Boulan and Pendergast, 1980), have been widely used to gain insights into sorting in polarized cells. The small DNA virus, simian virus 40, revealed new insights into the dynamics of caveolae and the delivery of their cargo to the (smooth) ER, apparently bypassing the Golgi complex (reviewed in Pelkmans and Helenius, 2002). Clearly, without studying viruses we would know far less about cells. Obviously, knowledge about cells also helps us to understand viruses. As viruses require many different cellular functions, understanding their life cycle requires understanding cells as a whole. Thus, among cell biologists, the ‘cell-virologist’ is necessarily an ‘all-rounder’.