Influenza

Peer-reviewed literature

2 March 2012

Pathogenesis and transmission of swine origin A(H3N2)v influenza viruses in ferrets

On 18 January 2012, the Proceedings of the National Academy of Sciences published a paper by Pearce et al.[1] which analysed the virulence, transmissibility and receptor-binding preference of four A(H3N2)v influenza viruses which originated in swine but were isolated from humans with uncomplicated upper respiratory tract illness. Of the four viruses characterized one was isolated in 2009 (KS/09), two in 2010 (MN/10, PA/10) and one in 2011 (IN/11). All four viruses replicated efficiently in the upper respiratory tract of ferrets that had been inoculated with 106 pfu of the viruses, all of which recovered fully from this infection. High viral titres were detected in the nasal passages of the ferrets inoculated with 2010-11 viruses, while KS/09 replicated efficiently throughout the respiratory tract. To assess transmissibility naïve ferrets were introduced to both the same cage as inoculated ferrets to study transmission by direct contact and adjacent cages with allowance for air flow to investigate their potential for respiratory droplet transmission. All four A(H3N2)v viruses transmitted efficiently in the direct contact model. MN/10, PA/09 and IN/11 transmitted efficiently in the respiratory droplet model although KS/09 transmission was delayed and did not spread to all naïve ferrets. A comparison of the hemaglutinin receptor binding site between KS/09, MN/10 and PA/10 showed that they were very similar and composed of characteristic residues found in human-adapted seasonal H3N2 viruses, including amino acids known to be critical in the binding of α2-6-sialylated glycans, a characteristic of human-adapted seasonal influenza viruses. Finally, the authors investigated the ability of the A(H3N2)v to replicate in cell cultures of human bronchial epithelium. Notably, all four viruses exhibited a 26- to 2,600-fold increase in replication at 48 hours post inoculation, compared with seasonal H3N2, demonstrating that the A(H3N2)v viruses replicate efficiently and to high titres in a model of human airway epithelial cells. The authors concluded that A(H3N2)v viruses have the capacity for efficient replication and transmission in mammals highlighting the need for continued public health surveillance of this emerging virus.

Comment:

This study has shed some light on the potential for A(H3N2)v viruses to cause sustained infection and transmission in human populations. As ferrets are the closest animal model available to demonstrate transmission in humans it suggests that A(H3N2)v viruses have potential for further spread. Indeed, the most recent outbreaks of A(H3N2)v included cases in which limited human-to-human transmission did occur [2,3]. However, human-to-human transmission of these particular viruses has so far occurred in settings such as day care centers which would facilitate ready transfer of infectious agents. Influenza A(H3N2) viruses now circulating in swine are related to and derived from viruses circulating in humans in the mid 1990s and recent studies have sought to understand the potential impact of an outbreak of A(H3N2)v by looking at population immunity to these viruses. Skowronski et al. using a related virus isolated from swine recently found that young adults had substantial levels of cross-reactive antibodies to this virus but that antibody titers were reduced in children and the adults over the age of 40 years[4]. This suggests that while some population immunity may exist, certain groups may be susceptible if the virus were to transmit widely. While the impact that they might have in human populations is unpredictable, human infections with swine-origin viruses have been detected more often in recent years though it is unclear whether this reflects increased surveillance or increased frequency of occurrence [5]. It is prudent, therefore, that human infections of swine-origin viruses continue to be investigated along with monitoring of animal herds.

Reference:

1. Pearce, M.B., Jayataman, A., Pappas, C., Belser, J.A., Zeng, H., Gustin, K.M., Maines, T.R., Sun, X., Raman, R., Cox, N.J., Sasisekharan, R., Katz, J.M., Tumpey, T.M. Pathogenesis and transmission of swine origin A(H3N2)v influenza viruses in ferrets. Proceedings of the National Academy of Sciences, 2012. br> 2. CDC. Limited human-to-human transmission of novel influenza A (H3N2) virus—Iowa, November 2011. MMWR 2011;60:1615–7.
3. CDC. Update: Influenza A (H3N2)v Transmission and Guidelines — Five States, 2011. 60(51);1741-1744.
4.Study Publication Review - Pathogenesis and transmission of swine origin A(H3N2)v influenza viruses in ferrets. Department of health and human services, CDC.
5. Skowronski, D.M., Serres, G.De., Janjua, N.Z., Gardy, J.L., Gilca, V., Dionne, M., Hamelin., M.E, Rhéaume, C., Boivin, G. Cross-reactive antibody to swine influenza A(H3N2) subtype virus in children and adults before and after immunization with 2010/11 trivalent inactivated influenza vaccine in Canada, August to November 2010. Euro Surveillance, 2012;17(4).

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