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. 2008 May 27;105(21):7558-63.
doi: 10.1073/pnas.0801259105. Epub 2008 May 27.

Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility

Jessica A Belser  1 , Ola Blixt, Li-Mei Chen, Claudia Pappas, Taronna R Maines, Neal Van Hoeven, Ruben Donis, Julia Busch, Ryan McBride, James C Paulson, Jacqueline M Katz, Terrence M Tumpey
Affiliations

Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility

Jessica A Belser et al. Proc Natl Acad Sci U S A. .

Abstract

Avian H7 influenza viruses from both the Eurasian and North American lineage have caused outbreaks in poultry since 2002, with confirmed human infection occurring during outbreaks in The Netherlands, British Columbia, and the United Kingdom. The majority of H7 infections have resulted in self-limiting conjunctivitis, whereas probable human-to-human transmission has been rare. Here, we used glycan microarray technology to determine the receptor-binding preference of Eurasian and North American lineage H7 influenza viruses and their transmissibility in the ferret model. We found that highly pathogenic H7N7 viruses from The Netherlands in 2003 maintained the classic avian-binding preference for alpha2-3-linked sialic acids (SA) and are not readily transmissible in ferrets, as observed previously for highly pathogenic H5N1 viruses. However, H7N3 viruses isolated from Canada in 2004 and H7N2 viruses from the northeastern United States isolated in 2002-2003 possessed an HA with increased affinity toward alpha2-6-linked SA, the linkage type found prominently on human tracheal epithelial cells. We identified a low pathogenic H7N2 virus isolated from a man in New York in 2003, A/NY/107/03, which replicated efficiently in the upper respiratory tract of ferrets and was capable of transmission in this species by direct contact. These results indicate that H7 influenza viruses from the North American lineage have acquired sialic acid-binding properties that more closely resemble those of human influenza viruses and have the potential to spread to naïve animals.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Glycan microarray analysis of Eurasian and North American lineage H7 influenza viruses. Analysis was performed on the following viruses: NL/219 (A), NL/230 (B), HK/486 (H5N1) (C), Rhea/NC (D), Can/504 (E), Can/444 (F), Tky/VA (G), Ck/Conn (H), and NY/107 (I). The glycan microarray was performed by using whole virus with antisera raised against homologous or cross-reactive virus as a primary antibody. Colored bars highlight glycans that contain α2–3 SA (yellow) and α2–6 SA (green). Error bars reflect the standard deviation in the signal for six independent replicates on the array. Structures of each of the numbered glycans are found in Table S1 (SI Text) and for selected glycans in Table 2.
Fig. 2.
Fig. 2.
Direct contact transmissibility of H7 influenza viruses. Three ferrets were inoculated with 107 EID50 of NL/219 (A), NL/230 (B), Tky/VA (C), Can/504 (D), NY/107 (E), or Ck/Conn (F) virus, and nasal washes were collected from each ferret on the indicated days p.i. (dark bars). A naïve ferret was placed in the same cage as each inoculated ferret 24 h p.i., and nasal washes were collected from each contact ferret on indicated days p.c. (light bars). The limit of virus detection was 101.5 EID50/ml.
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