Viruses are obligatory parasites that rely on the host biosynthetic machinery to replicate. In addition, they exploit numerous cellular processes for membrane trafficking, intra-cellular transport, as well as nuclear import and export. Accumulating evidence indicates that many viruses such as the vaccinia virus trigger their own endocytic uptake via cellular signalling pathways through specific interaction with host cells. This opens up a new field of research that elucidates the molecular determinants of these processes. Scientists on the EU-funded VIRNA (Cellular biology of virus infection) project wished to analyse the early steps in animal virus infection and identify the critical host cell proteins. For this purpose, they used high throughput screening by siRNA silencing and a broad spectrum of cellular and molecular biology techniques. They infected human cells in vitro with viruses of six different families (polyoma, alpha, pox, herpes, bunya, paramyxo, and myxoviruses) and monitored cellular and molecular changes. Project results helped researchers depict the strategies and diverse molecular mechanisms that enveloped and non-enveloped viruses employ to enter cells. Experimental evidence unveiled that apart from endocytosis, viruses become primed prior to penetration. Thousands of cellular proteins as well as viral genes seem to assist incoming viruses during entry, shedding of the viral envelope, initiation of transcription and replication. Collectively, the VIRNA work provided invaluable insight into the interaction between the incoming viruses and complex host cellular machinery and resulted in novel findings. Long term this knowledge could be exploited towards the design and development of new antiviral strategies.
Infection, virus, endocytosis, siRNA