In nearly all characterized influenza viruses, hemagglutinin (HA) is the 
receptor-binding protein while neuraminidase (NA) is a receptor-cleaving protein 
that aids in viral release. However, in recent years, several groups have 
described point mutations that confer receptor-binding activity on NA, albeit in 
laboratory rather than natural settings. One of these mutations, D151G, appears 
to arise in the NA of recent human H3N2 viruses upon passage in tissue culture. 
We inadvertently isolated the second of these mutations, G147R, in the NA of the 
lab-adapted A/WSN/33 (H1N1) strain while we were passaging a heavily engineered 
virus in the lab. G147R also occurs at low frequencies in the reported sequences 
of viruses from three different lineages: human 2009 pandemic H1N1 (pdmH1N1), 
human seasonal H1N1, and chicken H5N1. Here we reconstructed a representative 
G147R NA from each of these lineages and found that all of the proteins have 
acquired the ability to bind an unknown cellular receptor while retaining 
substantial sialidase activity. We then reconstructed a virus with the HA and NA 
of a reported G147R pdmH1N1 variant and found no attenuation of viral 
replication in cell culture or change in pathogenesis in mice. Furthermore, the 
G147R virus had modestly enhanced resistance to neutralization by the Fab of an 
antibody against the receptor-binding pocket of HA, although it remained 
completely sensitive to the full-length IgG. Overall, our results suggest that 
circulating N1 viruses occasionally may acquire the G147R NA receptor-binding 
mutation without impairment of replicative capacity.
IMPORTANCE: Influenza viruses have two main proteins on their surface: one 
(hemagglutinin) binds incoming viruses to cells, while the other (neuraminidase) 
helps release newly formed viruses from these same cells. Here we characterize 
unusual mutant neuraminidases that have acquired the ability to bind to cells. 
We show that the mutation that allows neuraminidase to bind cells has no 
apparent adverse effect on viral replication but does make the virus modestly 
more resistant to a fragment of an antibody that blocks the normal 
hemagglutinin-mediated mode of viral attachment. Our results suggest that 
viruses with receptor-binding neuraminidases may occur at low levels in 
circulating influenza virus lineages.