Influenza A Virus Neuraminidase Limits Viral Superinfection

Abstract

Enveloped viruses use multiple mechanisms to inhibit infection of a target cell by more than one virion. These mechanisms may be of particular importance for the evolution of segmented viruses, because superinfection exclusion may limit the frequency of reassortment of viral genes. Here, we show that cellular expression of influenza A virus neuraminidase (NA), but not hemagglutinin (HA) or the M2 proton pump, inhibits entry of HA-pseudotyped retroviruses. Cells infected with H1N1 or H3N2 influenza A virus were similarly refractory to HA-mediated infection and to superinfection with a second influenza A virus. Both HA-mediated entry and viral superinfection were rescued by the neuraminidase inhibitors oseltamivir carboxylate and zanamivir. These inhibitors also prevented the removal of ␣-2,3-and ␣-2,6-linked sialic acid observed in cells expressing NA or infected with influenza A viruses. Our data indicate that NA alone among viral proteins limits influenza A virus superinfection.

Virologic Differences Do Not Fully Explain the Diversification of Swine Influenza Viruses in the United States

“…This mirrors the results of other studies of reassortment between genetically similar viruses, in which increasing the time between infections reduced the incidence of coinfection and reassortment (22). One possible explanation for the decrease in viral superinfection over time is that infected cells export HA and NA to their cell surfaces, where NA cleaves surface sialic acids, thereby preventing other virus particles from binding to and infecting the same cells (28). Other mechanisms are also possible, however, such as induction of cellular antiviral responses.…”

Formation of virus-like particles from human cell lines exclusively expressing influenza neuraminidase

“…Furthermore, using a potent sialidase inhibitor and a point mutation (E262D) in NA that inactivates the catalytic site of the sialidase (Huang et al, 2008), we showed that NA activity was not necessary for the release of NA-VLPs in cells (Fig. 5).…”

“…A single amino acid change (E262D) in the NA is known to eliminate the sialidase activity of the NA molecule (Huang et al, 2008). HEK-293T cells were transfected with pcDNA-NA(H5) or pcDNA-NA(E262D), with or without pcDNA-HA.…”

Molecular Characterization on the Basis of Ha, Na and M Gene Revealed Changes in Critical Amino Acid Positions of Influenza a (H3n2) Virus Circulating in India During 2011-2013

“…Neuraminidase is a surface glyco protein and performs various functions like clearance of 'deceive' receptors within the respiratory mucin, decreased viral superinfection (Huang et al, 2008) and increased virus infectivity (Goto and Kawaoka, 1998 K369T, L370S, S372L, K385N, N387K, N402D and I464L were seen in all the samples. While K221E and I263V mutation was noted only in samples from 2012.…”