Viral entry mechanisms: the increasing diversity of paramyxovirus entry

Abstract

The paramyxovirus family contains established human pathogens such as the measles virus and human respiratory syncytial virus, as well as emerging pathogens including the Hendra and Nipah viruses and the recently identified human metapneumovirus. Two major envelope glycoproteins, the attachment protein and the fusion protein, promote the processes of viral attachment and virus-cell membrane fusion required for entry. Although common mechanisms of fusion protein proteolytic activation and the mechanism of membrane fusion promotion have been shown in recent years, considerable diversity exists in the family relating to receptor binding and the potential mechanisms of fusion triggering.

Figure 1. Schematic of paramyxovirus virion and surface glycoproteins

A) Schematic of a paramyxovirus; viral membrane shown in blue. B) Conserved domains of paramyxovirus fusion and attachment proteins. Domain abbreviations: fusion peptide (FP, orange); heptad repeat A (HRA, blue); heptad repeat B (HRB, red); transmembrane domain (TMD, black); cytoplasmic tail (C-Tail, dotted box); disulfide bond (S-S).

Figure 2. Potential mechanisms of paramyxovirus fusion protein triggering

Attachment protein shown with orange head domain and blue stalk, fusion protein shown in blue/green head domain and red stalk region, receptor shown in grey.

Figure 3. Models of lipid and protein fusion intermediates

A) Lipid intermediates culminating in the formation of a full fusion pore. B) Proposed fusion protein intermediates with subsequent formation of the post-fusion six-helix bundle. Fusion peptide,orange; heptad repeat A, blue; heptad repeat B, red; transmembrane domain, black.