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International audience; Membrane fusion is a fundamental biological process that allows different cellular compartments delimited by a lipid membrane to release or exchange their respective contents. Similarly, enveloped viruses such as alphaherpesviruses exploit membrane fusion to enter and infect their host cells. For infectious entry the prototypic human Herpes simplex viruses 1 and 2 (HSV-1 and -2, collectively termed HSVs) and the porcine Pseudorabies virus (PrV) utilize four different essential envelope glycoproteins (g): the bona fide fusion protein gB and the regulatory heterodimeric gH/gL complex that constitute the "core fusion machinery" conserved in all members of the Herpesviridae; and the subfamily specific receptor binding protein gD. These four components mediate attachment and fusion of the virion envelope with the host cell plasma membrane through a tightly regulated sequential activation process. Although PrV and the HSVs are closely related and employ the same set of glycoproteins for entry, they show remarkable differences in the requirements for fusion. Whereas the HSVs strictly require all four components for membrane fusion, PrV can mediate cell-cell fusion without gD. Moreover, in contrast to the HSVs, PrV provides a unique opportunity for reversion analyses of gL-negative mutants by serial cell culture passaging, due to a limited cell-cell spread capacity of gL-negative PrV not observed in the HSVs. This allows a more direct analysis of the function of gH/gL during membrane fusion. Unraveling the molecular mechanism of herpesvirus fusion has been a goal of fundamental research for years, and yet important mechanistic details remain to be uncovered. Nevertheless, the elucidation of the crystal structures of all key players involved in PrV and HSV membrane fusion, coupled with a wealth of functional data, has shed some light on this complex puzzle. In this review, we summarize and discuss the contemporary knowledge on the molecular mechanism of entry and membrane fusion utilized by the alphaherpesvirus PrV, and highlight similarities but also remarkable differences in the requirements for fusion between PrV and the HSVs.

Highlights ► Identification of nectin 4 as measles virus receptor for entry into epithelial cells. ► Identification of nucleolin as a broad entry receptor for the respiratory syncytial virus. ► Identification of the myelin oligodendrocyte glycoprotein as entry receptor for rubella virus. ► Identification of the natural resistance-associated macrophage protein as entry receptor for sindbis virus. ► Characterization of the interactions with DC-SIGN for entry into dendritic cells for phleboviruses and measles virus., The long-sought entry receptors for rubella, sindbis and respiratory syncytial viruses (RV, SV and RSV), together with the missing measles virus (MV) receptor for infection of epithelial cells, were identified in 2011. These have been major developments in the field of virus entry. In addition, 2011 was rich in new information about the interactions of MV, RSV and phleboviruses with DC-SIGN during infection of dendritic cells, a crucial step allowing the virus to breach the epithelial barrier and gain access to the lymph nodes. This faciliates dissemination to susceptible tissues where it can develop a vigorous and sustained replication, to eventually target specific organs from which it can propagate into the environment and efficiently infect new hosts, closing the merry-go-round of the virus cycle.

Publisher Summary This chapter describes the three-dimensional structure of rotavirus (RV) viral proteins 6 (VP6). The structural studies of VP6 by X-ray crystallography and by electron microscopy have led to a pseudo-atomic model of its helical assemblies and of the viral middle layer. Calculation of the surface electrostatic potential shows that VP6 is an acidic molecule, indicating that repulsion between capsomers is likely to be responsible for the different assemblies obtained at different pH. It also suggests that the inner shell of the viral particle plays an essential role in compensating the negative electrostatic charges of VP6. Protein VP6 plays a central role in the organization of the virion, acting as an adaptor between two distinct viral functions: cell entry (outer layer) and genomic RNA packaging (inner layer). It also seems to perform additional functions related to a possible concerted conformational switch of the viral particle necessary for transcription.