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| Reassortment is the mechanism where two different flu viruses infect the same cell simultaneously, and swap genetic material, producing a new, hybrid virus. |
#15,186
Influenza reassortment - also known as Antigenic Shift - is something we've discussed often in the blog, albeit mostly in birds, swine, and other mammals. This reshuffling of influenza genes is the primary force behind the creation of novel or pandemic flu (see NIAID Video: How Influenza Pandemics Occur).
While less commonly reported in humans, as any virologist will tell you; shift happens.
A little over 2 years ago, in Double-Whammied By Influenza, we looked at the relatively common occurrence of human dual infection with two types of flu - the prerequisite for reassortment. While there isn't a lot of research into these dual viral infections, they don't appear to produce significantly worse outcomes than influenza by itself.
Of course, YMMV (Your Misery May Vary).
Although we watch the evolution of avian and swine flu viruses with greatest concern, human seasonal flu viruses (H3N2 & H1N1) are fully capable of reassorting, and producing a novel flu subtype.
We don't see it happen often, but last May, in Denmark Reports Novel H1N2 Flu Infection, we saw the third Northern European report of a novel H1N2 (H1N1/H3N2) reassortment in just over a year (see also 2019 Swedish report and 2018 Netherlands case).The resultant novel H1N2 virus was unusual, but was deemed in February of 2019 as not posing a great risk by the CDC:
Risk Assessment:
This A(H1N2) reassortant virus is thought to pose a health risk similar to other seasonal influenza viruses. The virus has not been detected beyond this one person and current seasonal influenza vaccines would likely offer protection against this virus. Additionally, this virus does not have markers associated with resistance to the neuraminidase inhibitor class of antiviral drugs and, thus, should be susceptible to treatment with the currently recommended drugs oseltamivir, zanamivir and peramivir.
And indeed, we've seen novel H1N2 viruses circulate among humans before with little impact.
While a minor player in most regions, H1N2 was the predominant Influenza A(H1) virus reported during the UK's 2001–02 influenza season (cite).
Novel H3N2 viruses in humans, on the other hand, have almost exclusively come from swine-origin viruses (see CDC EID Journal: Locally Acquired Human Infection with Swine-Origin Influenza A(H3N2) Variant Virus, Australia, 2018).
All of which brings us to a CDC MMWR report, published yesterday, on the the discovery of the first seasonal human H3N2/H1N1 reassortment, detected last February in a teenage boy in Idaho.
Despite increased surveillance in the region, only one case has been detected. The evidence suggests this patient wasn't co-infected, and was therefore not the reassortant host. A finding which suggests the virus has some degree of transmissibility. Whether that is sustained or efficient is another matter.
Hopefully we'll see some kind of Risk Assessment from the CDC, and some follow up research on the transmissibility and virulence of this novel virus.
Even though we are dealing with a COVID-19 pandemic, this is yet another reminder that Nature's laboratory is open 24/7, and that we could easily be blindsided by another novel virus at any time.
Notes from the Field: Seasonal Human Influenza A(H3N2) and Influenza A(H1N1)pdm09 Reassortant Infection — Idaho, 2019
Weekly / April 10, 2020 / 69(14);427–428
Randi Pedersen, MPH1; Vonnita Barton1; Jennifer Tripp, MPH2; Lenee Blanton, MPH3; John Barnes, PhD3; Christine Hahn, MD1
PDF pdf icon[96K]
On February 17, 2019, a male patient aged 13 years with no underlying medical conditions was evaluated in an Idaho hospital emergency department for a 1-day history of fever (103°F [39.4°C]), dry cough, sore throat, headache, and weakness. A respiratory specimen was collected and tested positive for influenza A by rapid influenza diagnostic test (RIDT). The patient was treated with oseltamivir as an outpatient and recovered.
As part of routine surveillance, a second specimen collected during the emergency department visit on February 17 was forwarded to the Idaho Bureau of Laboratories (IBL), where CDC’s influenza reverse transcription–polymerase chain reaction (RT-PCR) diagnostic panel detected both pandemic influenza A and H3, which suggested an influenza A(H3N2) variant virus of swine origin.
The specimen was sent to CDC’s influenza diagnostic laboratory for confirmation, and the patient was interviewed.
During the week preceding illness onset, the patient did not travel and reported no animal exposure; he had not received a 2018–19 seasonal influenza vaccine. One household member developed respiratory symptoms on February 23, 2019, and sought care at an outpatient clinic, where a respiratory specimen tested positive for influenza A by RIDT. No specimen was available for additional testing, and no other exposures were identified. No additional household members reported respiratory symptoms.
Next generation sequencing at CDC revealed a new seasonal human influenza A(H3N2) and A(H1N1)pdm09 reassortant virus, rather than an influenza A(H3N2) variant virus of swine origin.
Reassortment occurs when two influenza viruses infect a single host cell and exchange gene segments, creating a new virus. Sequencing data suggested that the patient was not coinfected and that the reassortment event likely occurred in another person.
Phylogenetic analysis determined that the hemagglutinin genes belonged to human H3 subclade 3C.3a and neuraminidase genes belonged to human N2. Gene segments PB2, PB1, PA, NP, M, and NS displayed genetic similarity to human-origin influenza A(H1N1)pdm09 viruses.
Genetic markers that would confer reduced susceptibility to oseltamivir, peramivir, and zanamivir were not detected. Viruses in H3 subclade 3C.3a react poorly by focus reduction assay with ferret antisera raised against A/Singapore/INFMH-16–0019/2016(3C.2a1), signifying that the 2018–19 Northern Hemisphere influenza vaccine* might not be protective against this virus.
As part of enhanced surveillance, the hospital where the patient sought care forwarded an additional 45 specimens that tested positive by RIDT for influenza A, collected during January 1–April 27, 2019, to IBL. Using the CDC influenza RT-PCR diagnostic panel, IBL determined that 23 (51.1%) were influenza A(H1N1)pdm09, 13 (28.9%) were influenza A(H3N2), and influenza was not detected in nine (20.0%) specimens. IBL sent 17 of the 45 specimens to CDC for sequencing; no additional reassortant viruses were identified.
At the time of the patient’s illness onset, influenza A(H1N1)pdm09 and A(H3) were cocirculating in Idaho (Figure), increasing the likelihood of coinfection and reassortment. Influenza A reassortment is observed at high rates in animal and cell culture models, but a biologically successful human reassortant virus is rarely reported (1–3).
This is CDC’s first detection of this type of seasonal human influenza A(H3N2) and influenza A(H1N1)pdm09 reassortment. CDC recommends that state and local health departments, hospitals, and clinicians maintain surveillance to identify patients who might be transmitting newly emerging influenza viruses.†,§ CDC will continue virologic surveillance to monitor influenza genetic evolution and inform vaccine strain selection.
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