An 18-amino acid deletion in an influenza neuraminidase

Influenza neuraminidase

“…There is no information on whether all these canonical Asn-X-Ser/Thr sites are glycosylated. Most NAs have stalks of approximately 50 amino acids, but deletions of up to 18 amino acids have been found in N1 and N2 NA stalks 15,16 . The cryo-EM study of A/Aichi/68 virions showed a 51-amino acid stalk extending 10 nm from the viral membrane 10 .…”

“…A helix would extend 7.6 nm, so the stalk structure must be more extended than a helix. Secondary structure programs such as JPred 17 do not predict any helices or coiled-coils, but show about 50% beta sheets in the full-length stalks, and measurements of full-length versus deleted stalk also indicated a mixture of extended and folded structure 16 . Several studies have associated deletions in the stalks of N1 NA of avian viruses with transmission from ducks to land-based poultry (an excellent literature review is given by Munier et al 18 ), but the mechanism remains obscure.…”

“…The activity of NA for small substrates is unchanged by the deletion, but activity with complex substrates is reduced 16,18 , suggesting that lower accessibility and hence lower activity is an advantage for viruses replicating in chickens compared to those of waterfowl. The full-length NA extends 2 nm beyond the HA from the viral membrane 10 while the “stubby” variant with a deletion in the stalk was reduced 2.5 nm 16 , putting its sialic acid binding site at the same level or just below the HA binding site. Studies of HA binding specificity and affinity to sialic acids presented on a glycan array have shown that sialic acid binding by the HA is highly dependent on sugar conformation and extension 19,20 .…”

Amino Acid 316 of Hemagglutinin and the Neuraminidase Stalk Length Influence Virulence of H9N2 Influenza Virus in Chickens and Mice

“…H5 and H7 influenza viruses with a shortened NA stalk are typically selected in chickens (18)(19)(20)(21). An early study found that a spontaneous NA mutant with an 18-amino-acid deletion in the stalk had deficient enzyme activity and did not efficiently release influenza virus from erythrocytes (9). Moreover, the A/WSN/33 (H1N1) virus, which lacks the stalk region, cannot grow in eggs, is inefficiently eluted from erythrocytes, and is highly attenuated in mice compared with viruses with a long NA stalk (8).…”

“…Previous studies showed that NA stalk length affects the release of viruses bound to erythrocytes (8,9); thus, elution of these recombinant viruses with short or long stalk NAs from erythrocytes was compared, as described previously (8). Briefly, viruses were absorbed on chicken erythrocytes at 4°C for 1 h, and release at 37°C was monitored for 5 h. Elution of the SD16-⌬NA and SD16-HA316S/⌬NA short stalk viruses was complete after 5 h of incubation (Fig.…”