Impact of a large deletion in the neuraminidase protein identified in a laninamivir‐selected influenza A/Brisbane/10/2007 (H3N2) variant on viral fitness in vitro and in ferrets

Abstract

Viral fitness of a laninamivir‐selected influenza A/Brisbane/10/2007‐like (H3N2) isolate (LRVp9) containing a 237‐amino acid neuraminidase deletion and a P194L hemagglutinin mutation was evaluated in vitro and in ferrets. LRVp9 and the wild‐type (WT) virus showed comparable replication kinetics in MDCK‐ST6GalI cells. Cultured virus was recovered between days 2 and 5 post‐infection in nasal washes (NW) from the 4 WT‐infected ferrets whereas no virus was recovered from the LRVp9‐infected animals. There was a ≥1 log reduction in viral RNA copies/μl of NW for LRVp9 compared to WT at most time points. The large neuraminidase deletion compromises viral infectivity in vivo.

Replication and transmission of an influenza A(H3N2) virus harboring the polymerase acidic I38T substitution, in guinea pigs.

“…The supernatants were harvested at 12, 24, 48, 72 and 96 h post-infection (h.p.i.) and used for quantification of viral RNA using an influenza qPCR test [24] and viral titration by TCID 50 ml −1 in ST6GalI-MDCK cells.…”

Bat-Borne Influenza A Viruses: An Awakening

“…Although an explanation for the selection of truncated N11 NA is still lacking, it is tempting to speculate that the negatively charged N11 NA head domain might disturb proper H18 HA-mediated entry caused by repulsions with the also negatively charged cellular membrane. Importantly, even though NA-negative mutants have been described for classical IAVs before, the ability of H18N11 to compensate for the lack of a functional NA without impaired viral growth in vitro and in vivo is unprecedented among all other known classical subtypes of influenza (Hughes et al 2000;Kalthoff et al 2013;Samson et al 2014;Ann et al 2016). Whether H17N10 possesses a comparable N10 NA-independent replication capacity remains to be determined.…”