The highly pathogenic H 7 N 3 avian influenza strain from July 2012 in Mexico acquired an extended cleavage site through recombination with host 28 S rRNA

Background: A characteristic difference between highly and non-highly pathogenic avian influenza strains is the presence of an extended, often multibasic, cleavage motif insertion in the hemagglutinin protein. Such motif is found in H7N3 strains from chicken farm outbreaks in 2012 in Mexico. Methods: Through phylogenetic, sequence and structural analysis, we try to shed light on the role, prevalence, likelihood of appearance and origin of the inserted cleavage motifs in these H7N3 avian influenza strains. Results: The H7N3 avian influenza strain which caused outbreaks in chicken farms in June/July 2012 in Mexico has a new extended cleavage site which is the likely reason for its high pathogenicity in these birds. This cleavage site appears to have been naturally acquired and was not present in the closest low pathogenic precursors. Structural modeling shows that insertion of a productive cleavage site is quite flexible to accept insertions of different length and with sequences from different possible origins. Different from recent cleavage site insertions, the origin of the insert here is not from the viral genome but from host 28S ribosomal RNA (rRNA) instead. This is a novelty for a natural acquisition as a similar insertion has so far only been observed in a laboratory strain before. Given the abundance of viral and host RNA in infected cells, the acquisition of a pathogenicity-enhancing extended cleavage site through a similar route by other low-pathogenic avian strains in future does not seem unlikely. Important for surveillance of these H7N3 strains, the structural sites known to enhance mammalian airborne transmission are dominated by the characteristic avian residues and the risk of human to human transmission should currently be low but should be monitored for future changes accordingly. Conclusions: This highly pathogenic H7N3 avian influenza strain acquired a novel extended cleavage site which likely originated from recombination with 28S rRNA from the avian host. Notably, this new virus can infect humans but currently lacks critical host receptor adaptations that would facilitate human to human transmission. Background Influenza viruses are classified into 3 different types (A,B,C) and influenza A is further divided into specific subtypes named after the respective combination of surface protein variants pairing 1 of 17 hemagglutinins (the “H” in HxNx) with 1 of 10 neuraminidases (the “N” in HxNx). These subtypes are known to circulate preferably in specific bird species which possess sialic acid linked to oligosaccharides via alpha (2,3) linkages, such as chickens, turkeys, and ducks. [1,2]. There has been a recent outbreak of a new H7N3 strain in chicken farms in Mexico in June/July 2012, characterized as a highly pathogenic avian influenza (HPAI) strain [3]. While the epidemiological and initial genetic characterization of this outbreak strain has been described elsewhere [4,5], we would like to add information on the detailed origin of the extended cleavage site possibly responsible for making the strain highly * Correspondence: sebastianms@bii.a-star.edu. sg Equal contributors Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore National Public Health Laboratory, Communicable Diseases Division Ministry of Health, Singapore, Singapore Full list of author information is available at the end of the article © 2013 Maurer-Stroh et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Maurer-Stroh et al. Virology Journal 2013, 10:139 http://www.virologyj. com/content/10/1/139