Monday, August 28, 2017

Virology: Detection & Characterization Of Avian H4N6 In Midwestern Swine (2015)


Avian Low path (LPAI) H4N6 viruses commonly circulate in aquatic birds around the globe, including in North America. They cause little or no illness in their natural avian reservoir  hosts, are only rarely reported in domestic poultry, and so far have little or no track record of human infection.
At first glance, this subtype appears fairly benign.  But, the one constant in influenza is change, and in recent years we've seen some changes in H4N6

Eighteen years ago (1999) avian H4N6 was first detected in mammalian hosts among Canadian swine. The following year, this report appeared in the Journal of Virology.
J Virol. 2000 Oct;74(19):9322-7.

Isolation and characterization of H4N6 avian influenza viruses from pigs with pneumonia in Canada.
Karasin AI1, Brown IH, Carman S, Olsen CW.


In October 1999, H4N6 influenza A viruses were isolated from pigs with pneumonia on a commercial swine farm in Canada. Phylogenetic analyses of the sequences of all eight viral RNA segments demonstrated that these are wholly avian influenza viruses of the North American lineage. To our knowledge, this is the first report of interspecies transmission of an avian H4 influenza virus to domestic pigs under natural conditions.
In 2002, the USDA published:
Pathogenesis of H4N6 Influenza A Virus Infection in Pigs and Turkeys: A Newly Emerging Disease Concern
Objective:Two isolates of H4N6 influenza A viruses were recently recovered from pigs with pneumonia in Canada. These were the first H4N6 subtype viruses ever isolated from naturally infected pigs. Our genetic analyses revealed these to be wholly avian viruses, but despite their avian lineage, preliminary research results have demonstrated that they can spread from pig-to-pig

Furthermore, additional results have shown that they preferentially bind to SAL2,6Gal molecules, which is the receptor type present in human tracheal cells, rather than the SAL2,3Gal receptors utilized by avian viruses. Given this finding and the fact that our swine and human populations are both immunologically naive to H4 viruses, these viruses pose an emerging disease concern for both veterinary and human health.
         (Continue . . . )

Pigs are susceptible to a range of human, swine, and avian flu viruses, and possess both avian-like (SAα2,3Gal) and human-like (SAα2,6Gal) receptor cells in their respiratory tract, making them potential`mixing vessels' for influenza reassortment. 
Over the past decade we've seen a number of brief references to H4N6 in mammalian hosts, including North American Raccoons, Raccoons in Japan, Chinese pigs, and seals.   
Three weeks ago, in Cell: Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4, researchers presented evidence that avian H4N6 viruses can adapt to human receptor cells while in a swine host (using the 1999 Ontario isolate), warning:
These results clearly implicate the potential threat posed by H4 viruses to public health. Therefore, early-warning study of H4 subtype human receptor-binding property is highly appreciated.

All of which leads us to a new study, published last week in the Virology journal, detailing the first discovery (in 2015) of avian H4N6 in swine from America's Midwest.
Detection and characterization of an H4N6 avian-lineage influenza A virus in pigs in the Midwestern United States
Eugenio J. Abentea, Phillip C. Gaugerb, Rasna R. Waliaa, Daniela S. Rajaoa, 1, Jianqiang Zhangb, Karen M. Harmonb, Mary Lea Killianc, Amy L. Vincenta, , rights and content

  • An avian H4N6 influenza A virus was detected and isolated from a pig in Midwestern United States
  • Analysis of clinical samples suggests the H4N6 virus was not widespread in swine
  • The H4N6 replicated efficiently in the lungs of challenged pigs and caused lesions.
  • Virus was not detected in the upper respiratory tract of challenged pigs.
  • There was no evidence of transmission in contact pigs exposed to challenged pigs.

H4Nx viruses were reported in swine in Canada and China, but had not been recognized in swine in the USA. In late 2015, an avian-origin H4N6 influenza A virus was isolated from pigs in the United States during a routine diagnostic investigation of clinical respiratory disease in the herd. 

Serological analysis from additional pigs at the farm and other pigs within the swine production system indicated that the virus did not efficiently transmit from pig-to-pig and the mode of transmission to swine could not be determined. The isolate was characterized at the molecular level and the pathogenesis and transmission was experimentally evaluated in pigs. 
Although the virus replicated in the lungs of pigs and caused mild pulmonary lesions, there was no evidence of replication in the upper respiratory tract or transmission to indirect contacts, supporting the findings on the farm.
Although this avian H4N6 virus appears far from being ready for prime time, and its current pathogenicity in humans appears marginal, by circulating in pigs it also provides additional unique genetic `building blocks' for reassortment with swine, human, or other avian influenza viruses.
Since avian H4N6 is just one of many non-swine viruses jumping to pigs (see below), the concern is this mix and match style of evolution will eventually produce a viable subtype with genuine pandemic potential.
For other recent swine reassortant related blogs, you may wish to revisit:
J. Virology: A Single Amino Acid Change Alters Transmissability Of EAH1N1 In Guinea Pigs

I&ORV: Triple-Reassortant Novel H3 Virus of Human/Swine Origin Established In Danish Pigs
Emerg. Microbes & Inf.: Pathogenicity & Transmission Of A Swine Influenza A(H6N6) Virus - China

Sci Rpts:Reassorted H9N2:pH1N1 Virus Transmission After Serial Passage In Swine