Paramyxoviruses Turn Paradigms Upside Down

Paramyxoviruses cause respiratory tract diseases such as croup and pneumonia, as well as measles and mumps. The envelope proteins of these viruses share some features in common with influenza and retroviruses. These similarities include a precursor protein that is cleaved into two fragments, the second of which, called El, bears a fusion peptide at its amino terminus. In addition, peptides from the paramyxovirus FI proteins assemble into stable helical bundles resembling HIV gp41 and influenza HA2 (Baker et al, 1999 Lawless-Delmedico et al, 2000 Zhao et al, 2000). The paramyxovirus F protein differs from influenza HA and retroviral TM 

The authors of the NDV-F structure propose that they have crystallized a mixture of the native and sprung forms of the spike protein, and that these two versions are similar enough structurally to pack into the same crystal lattice (Chen et al., 2001a). In light of the enormous structural changes that are observed on exposure of influenza HA to low pH, the possibility that minimal conformational changes occur in paramyxoviruses is remarkable. Furthermore, the long central helix of NDV-F is proposed to point in the opposite direction from that of influenza HA, such that extension of the central coiled coil sends the fusion peptides in the direction of the virus membrane (Fig. 12). 

Although the NDV-F structure is provocative, it is not clear to which functional state the structure truly corresponds. Even assuming that the trace of the polypeptide chain faithfully represents the conformation of the majority of the molecules in the crystals, there are reasons to suspect that this structure may not be the native state of the protein. In particular, electron microscopy of another paramyxovirus F protein revealed a 

Although there are mechanistic differences between retroviruses, paramyxoviruses, and the orthomyxovirus influenza, the viruses discussed to this point have definite structural and functional similarities including spikelike, trimeric native structures and the presence of coiled coils in their fusion-active subunits. The flaviviruses and alphaviruses, however, appear to be another class of enveloped viruses entirely. Flaviviruses include yellow fever. West Nile virus. Dengue virus, and tick-borne encephalitis virus (TBEV). Alphaviruses, of the togavirus family, include 

These structural studies on the alphavirus and flavivirus membrane fusion proteins strengthen the relationship between these virus families, but apparently distance them from the trimeric influenza and retrovirus envelope assemblies. However, low pH specifically triggers not only a conformational change in alphavirus and flavivirus surface proteins, but also an oligomerization switch to a trimeric state (Allison et ah, 1995). This 

---