Paramyxoviruses crossing the host membrane: mechanisms for entry

Abstract

The paramyxovirus family is a group of enveloped, negative-strand RNA viruses that includes common and highly infectious human pathogens such as mumps, measles, respiratory syncytial virus, human metapneumovirus and the closely related, highly lethal zoonotic Hendra and Nipah viruses. Paramyxoviruses are unique in that they have two envelope glycoproteins that mediate virion binding and membrane fusion, instead of a single glycoprotein that fulfills both functions. The following text provides a review on how the two paramyxovirus glycoproteins, the attachment protein and fusion protein, interact with each other, and to which host-cell receptors they bind, to ensure membrane fusion and entry into the host cell. In the Paramyxovirinae subfamily, binding of the attachment protein to an entry receptor triggers the fusion protein, which in turn drives membrane fusion. While biochemical studies and recently solved crystal structures have shed some light on this process, the exact mechanism by which the attachment protein triggers the fusion protein upon receptor binding, remains to be elucidated for any of the Paramyxovirinae. In the Pneumovirinae subfamily on the other hand, the attachment protein is not necessary to achieve membrane fusion and the fusion protein mediates receptor binding as well as membrane fusion. The current view is that virus entry in vivo is a highly dynamic process that involves a complex interaction between viral glycoproteins on the one hand and host cell receptors on the other. Furthermore, individual paramyxovirus species might employ multiple entry pathways, using more than one type of receptor, relying on fusion at the plasma membrane as well as on fusion after endocytosis.