Increased Acid Stability of the Hemagglutinin Protein Enhances H5N1 Influenza Virus Growth in the Upper Respiratory Tract but Is Insufficient for Transmission in Ferrets

• DOI: 10.1128/jvi.01175-13
• Publication Date: 2013-07-04T08:20:19Z
• Authors: Hassan Zaraket; Olga A. Bridges; Susu Duan; Tatiana Baranovich; Sun-Woo Yoon; Mark L. Reed; Rachelle Salomon; Richard J. Webby; Robert G. Webster; Charles J. Russell
• Keywords: Respiratory tract

Influenza virus entry is mediated by the acidic-pH-induced activation of hemagglutinin (HA) protein. Here, we investigated how a decrease in HA pH (an increase acid stability) influences properties highly pathogenic H5N1 influenza mammalian hosts. We generated isogenic A/Vietnam/1203/2004 (H5N1) (VN1203) viruses containing either wild-type protein (activation 6.0) or an HA2-K58I point mutation (K to I at position 58) 5.5). The VN1203-HA2-K58I had replication kinetics similar those VN1203 MDCK and normal human bronchial epithelial cells yet reduced growth alveolar A549 cells, which were found have higher endosomal than cells. Wild-type promoted levels morbidity mortality C57BL/6J mice ferrets, neither transmitted efficiently naive contact cage-mate ferrets. acid-stabilizing mutation, diminishes transmission ducks, increased load ferret nasal cavity early during infection while simultaneously reducing lungs. Overall, single, was enhance upper respiratory tract, it insufficient enable ferrets absence additional mutations that confer α(2,6) receptor binding specificity remove critical N-linked glycosylation site. information provided here on contribution stability fitness transmissibility mammals background non-laboratory-adapted provides essential for surveillance assessment pandemic potential currently circulating viruses.