Alternative conformations of a major antigenic site on RSV F

Jones, Harrison G.; Battles, Michael B.; Lin, Chun-Chi; Bianchi, Siro; Corti, Davide; McLellan, Jason S.

RSV is an enveloped virus of the Pneumoviridae family and it has a single-stranded, negative-sense RNA genome. There are two subtypes of RSV, A and B, to which many individual strains belong. RSV has two major glycoproteins on the viral surface important for entry: the fusion (F) and attachment (G) glycoproteins [7] . Whereas RSV G is the primary source of sequence variation and defines the subtype of a specific virus, the fusion glycoprotein is well conserved with sequence identities >90% [8] . RSV F is a class I fusion glycoprotein initially produced as an inactive precursor, F0, that is subsequently cleaved by furin-like proteases to generate a protomer of disulfide-linked subunits, F1 and F2 [9] [10] [11] [12] . Three of these protomers associate to form the functional trimeric glycoprotein required for membrane fusion and infection [13] [14] [15] . Numerous vaccine trials for RSV are currently underway [16] , many of which contain the RSV F glycoprotein as an antigen because it has been shown that F is a major target of neutralizing antibodies [17, 18] and is the only protein on the viral surface that is strictly required for entry [19, 20] .