Paramyxovirus Fusion and Entry: Multiple Paths to a Common End

Abstract

The paramyxovirus family contains many common human pathogenic viruses, including measles, mumps, the parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and the zoonotic henipaviruses, Hendra and Nipah. While the expression of a type 1 fusion protein and a type 2 attachment protein is common to all paramyxoviruses, there is considerable variation in viral attachment, the activation and triggering of the fusion protein, and the process of viral entry. In this review, we discuss recent advances in the understanding of paramyxovirus F protein-mediated membrane fusion, an essential process in viral infectivity. We also review the role of the other surface glycoproteins in receptor binding and viral entry, and the implications for viral infection. Throughout, we concentrate on the commonalities and differences in fusion triggering and viral entry among the members of the family. Finally, we highlight key unanswered questions and how further studies can identify novel targets for the development of therapeutic treatments against these human pathogens.

Hemagglutinin homologue from H17N10 bat influenza virus exhibits divergent receptor-binding and pH-dependent fusion activities

“…Influenza C virus is exemplary for interaction with an alternative receptor in that it uses a unique sialic acid, 9-O-acetyl-N-acetylneuraminic acid, for virus entry, and 9-O-acetyl esterase activity instead of NA activity to destroy receptors for virus release (20). However, the H17N10 virus may bind a radically different receptor, such as a protein receptor (21), as seen for other bat viruses that have converted sialic acid binding sites into protein binding sites (22). To date, all attempts to propagate the bat H17N10 viruses in embryonated chicken eggs and several mammalian cells have been unsuccessful.…”

Antiviral activity of mycosynthesized silver nanoparticles against herpes simplex virus and human parainfluenza virus type 3

“…Their mechanism of penetra tion into cells presents several common features; nevertheless they present profound differences in the structural organization of fusion glycoproteins. 45,46 AgNPs have shown antiviral efficacy against several viruses regardless of the specific structural details of each single family, so may provide the opportunity for developing broad-spectrum antiviral drugs. Nonenveloped viruses are also putative targets of AgNPs, since their exposed capsid surfaces are constituted by proteins that serve as receptor-binding molecules, but no relevant data are as yet available in the literature.…”

Morbillivirus and henipavirus attachment protein cytoplasmic domains differently affect protein expression, fusion support and particle assembly

“…These structures reveal a common architecture where the b-sheets of the globular head are arranged symmetrically around a central axis as a six-bladed propeller. The attachment protein-mediated initiation of the F protein rearrangement and subsequent membrane fusion seem to be highly conserved, despite widely diverse receptors (Chang & Dutch, 2012). Interaction with the respective cellular receptors induces conformational changes in the attachment protein globular head (Bose et al, 2012;Liu et al, 2013;Navaratnarajah et al, 2011), which are in turn transferred to the stalk region (Bose et al, 2011;Liu et al, 2013Liu et al, , 2015Navaratnarajah et al, 2012;Yuan et al, 2011).…”