Some animal influenza A viruses (IAVs) bind not only to N-acetylneuraminic acid 
(Neu5Ac) but also to N-glycolylneuraminic acid (Neu5Gc), which has been 
discussed as a virus receptor. Human cells cannot synthesize Neu5Gc due to 
dysfunction of the CMP-Neu5Ac hydroxylase (CMAH) gene, which converts CMP-Neu5Ac 
to CMP-Neu5Gc. However, exogenous Neu5Gc from Neu5Gc-rich dietary sources is 
able to be metabolically incorporated into surfaces of tissue cells and may be 
related to enhancement of the infectivity and severity of IAV. Here, we 
investigated the receptor function of Neu5Gc on IAV infection in 
Neu5Gc-expressing cells by transfection of the monkey CMAH gene into human cells 
or by incubation with human cells in the presence of N-glycolylmannosamine. 
Expression of Neu5Gc on human cells clearly suppressed infectivity of IAVs that 
possess Neu5Gc binding ability. Furthermore, there was no difference in 
infectivity of a transfectant virus that included the wild-type HA gene from 
A/Memphis/1/1971 (H3N2), which shows no Neu5Gc binding, between parent MCF7 
cells and cells stably expressing the monkey CMAH gene (CMAH-MCF7 cells). On the 
other hand, cell entry of the transfectant virus that included the 
Neu5Gc-binding HA gene with a single mutation to Tyr at position Thr155 was 
arrested at the stage of internalization from the plasma membrane of the 
CMAH-MCF7 cells. These results indicate that expression of Neu5Gc on the surface 
of human epithelial cells suppresses infection of IAVs that possess Neu5Gc 
binding ability. Neu5Gc is suggested to work as a decoy receptor of 
Neu5Gc-binding IAVs but not a functional receptor for IAV infection.
IMPORTANCE: Influenza A viruses (IAVs) bind to the host cell surfaces through 
sialic acids at the terminal of glycoconjugates. For IAV binding to sialic 
acids, some IAVs bind not only to N-acetylneuraminic acid (Neu5Ac) as a receptor 
but also to N-glycolylneuraminic acid (Neu5Gc). Neu5Gc has been discussed as a 
receptor of human and animal IAVs. Our results showed that Neu5Gc expression on 
human epithelial cells suppresses infection of IAVs that possess Neu5Gc binding 
ability. Neu5Gc is suggested to be a "decoy receptor" of Neu5Gc-binding IAVs but 
not a functional receptor for IAV infection. Human cells cannot synthesize 
Neu5Gc because of dysfunction of the CMP-N-acetylneuraminic acid hydroxylase 
gene but can exogenously and metabolically incorporate Neu5Gc from dietary 
sources. The expression of Neu5Gc on human epithelial cells by taking in 
exogenous Neu5Gc from Neu5Gc-rich dietary sources may be related to restriction 
of the infection of IAVs that have acquired Neu5Gc binding ability.