Monday, July 09, 2018

J. Virology: Pathogenesis & Transmission of H3N2v Viruses Isolated in the United States, 2011-2016


In the fall of 2011 a new strain of swine H3N2 (see graphic above) was found to have evolved in American pigs. What set this virus apart from earlier swine H3N2 viruses was that it was a triple reassortant swine virus which had picked up (via reassortment) the matrix (M) gene from the 2009 H1N1 pandemic virus.

The following year, the CDC would speculated that:
`This M gene may confer increased transmissibility to and among humans, compared to other variant influenza viruses.’CDC HAN 2012
We first learned of this new strain via an early release from the CDC’s MMWR, which described two young children – one in Indiana and another in Pennsylvania - who were infected by a novel H3N2 virus (see Swine-Origin Influenza A (H3N2) Virus Infection in Two Children --- Indiana and Pennsylvania, July--August 2011).

The MMWR report stated:
No epidemiologic link between the two cases has been identified, and although investigations are ongoing, no additional confirmed human infections with this virus have been detected. 
Within days, however, Pennsylvania Reported 2 More Novel Flu Cases.  On September 9th, 2011 the CDC updated their SOIV (Swine Origin Influenza Virus) page (see CDC Update On Recent Novel Swine Flu Cases), acknowledging the possibility that limited human-to-human transmission of this trH3N2 virus might be occurring.
By the end of 2011, 12 cases had been reported across 5 states.  
Since the influenza subtypes that commonly circulate in swine (H1, H2 & H3) are similar to those that have caused all of the human pandemics going back 130 years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), we pay close attention whenever a swine flu virus manages to jump - even in a limited way - to humans.
As a precaution - in December of 2011 the CDC announced their intention of Developing A trH3N2 Seed Vaccine.
The following year (2012) more than 300 swine `variant’ infections were confirmed (see A Variant Swine Flu Review) across 12 states, mostly linked to attendance of state and county fairs. Based on published studies, this was likely a substantial undercount (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012)
While we've seen a handful of H1N1v & H1N2v viruses also jump to humans, H3N2v has been by far the most common, making up more than 90% of all reported cases. 
H3N2 Variant:[A/Indiana/08/11] is among the 16 novel viruses currently being  tracked by the CDC's IRAT (Influenza Risk Assessment Tool) Rankings, and while its severity would likely be low-to-moderate, it has the third highest `emergence score' (n=6.0) on their list. 

Since 2011, H3N2v has continued to evolve, diversify, and form new genotypes (see MMWR: Investigation Into H3N2v Outbreak In Ohio & Michigan - Summer 2016). And each of these variants is on their own evolutionary path.
With the announcement 9 days ago of the first reported H3N2v case of 2018 (see CDC FluView & Statement On Indiana H3N2v Case), this seems an opportune time to look at another recent research study on this virus.
From the Journal of Virology, and authored by researchers from the CDC and Emory University, we have the following look at this emerging swine variant virus. The full study is behind a pay wall, but the abstract provides the gist.

Pathogenesis and transmission of genetically diverse swine-origin H3N2v influenza A viruses from multiple lineages isolated in the United States, 2011-2016

Xiangjie Sun1, Joanna A. Pulit-Penaloza1, Jessica A. Belser1, Claudia Pappas1, Melissa B. Pearce1, Nicole Brock1, Hui Zeng1, Hannah M. Creager1,2, Natosha Zanders1, Yunho Jang1, Terrence M. Tumpey1Todd Davis1 and Taronna R. Maines1*

+ Author Affiliations
1Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, U.S.A. 30329
2Emory University, Atlanta, GA, U.S.A.


While several swine-origin influenza A H3N2 variant (H3N2v) viruses isolated from humans prior to 2011 have been previously characterized for their virulence and transmissibility in ferrets, recent genetic and antigenic divergence of H3N2v viruses warrants an updated assessment of their pandemic potential.
Here, four contemporary H3N2v viruses isolated during 2011-2016 were evaluated for their replicative ability in both in vitro and in vivo mammalian models, as well as their transmissibility among ferrets. 

We found that all four H3N2v viruses possessed similar or enhanced replication capacity in a human bronchial epithelium cell line (Calu-3) compared to a human seasonal influenza virus, suggestive of strong fitness in human respiratory tract cells. 

The majority of H3N2v viruses examined in our study were mildly virulent in mice and capable of replicating in mouse lungs with different degrees of efficiency. In ferrets, all four H3N2v viruses caused moderate morbidity and exhibited comparable titers in the upper respiratory tract, but only 2 of the 4 viruses replicated in the lower respiratory tract in this model. Furthermore, despite efficient transmission among cohoused ferrets, recently isolated H3N2v viruses displayed considerable variance in their ability to transmit by respiratory droplets. 

The lack of a full understanding of the molecular correlates of virulence and transmission underscores the need for close genotypic and phenotypic monitoring of H3N2v viruses and the importance of continued surveillance to improve pandemic preparedness.

Importance: Swine-origin influenza viruses of the H3N2 subtype, with the HA and NA derived from historic human seasonal influenza viruses, continue to cross species barriers and cause human infections, posing an indelible threat to public health. 

To help us better understand the potential risk associated with swine-origin H3N2v viruses that emerged in the U.S between 2011-2016 influenza seasons, we use both in vitro and in vivo models to characterize the ability of these viruses to replicate, caused disease, and transmit in mammalian hosts.
The efficient respiratory droplet transmission exhibited by some of the H3N2v viruses in the ferret model combined with the existing evidence of low immunity against such viruses in young children and older adults highlights their pandemic potential. 
Extensive surveillance and risk assessment of H3N2v viruses should continue to be an essential component of our pandemic preparedness strategy.

You may recall that a few months ago, in J. Virology: Analysis Of A Swine Variant H1N1 Virus Associated With A Fatal Outcome, we looked at a study by many of these same authors on the genetics, infectivity and transmissibility (in ferrets) of a different swine variant subtype that caused the death of the patient in Ohio in 2015.
Although rare, the prime `season' for swine variant flu appears to be from early summer and into the fall, when millions of people visit agricultural exhibits held by state and country fairs across the country.
Despite the current low risk of infection, there are some things you should consider doing to reduce your chances of getting sick, particularly if you are at `high risk' of flu complications.  This from the CDC.
CDC Recommendations For People At High Risk:
  • If you are at high risk of serious flu complications and are going to a fair where pigs will be present, avoid pigs and swine barns at the fair. This includes children younger than 5 years, people 65 years and older, pregnant women, and people with certain long-term health conditions (like asthma, diabetes, heart disease, weakened immune systems, and neurological or neurodevelopmental conditions).
If you are not at high risk, take these precautions:
  • Don’t take food or drink into pig areas; don’t eat, drink or put anything in your mouth in pig areas.
  • Don’t take toys, pacifiers, cups, baby bottles, strollers, or similar items into pig areas.
  • Wash your hands often with soap and running water before and after exposure to pigs. If soap and water are not available, use an alcohol-based hand rub.
  • Avoid close contact with pigs that look or act ill.
  • Take protective measures if you must come in contact with pigs that are known or suspected to be sick. This includes wearing personal protective equipment like protective clothing, gloves and masks that cover your mouth and nose when contact is required.
  • To further reduce the risk of infection, minimize contact with pigs in the pig barn and arenas.

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