Nature: Reverse Zoonosis of the 2022–2023 Human Seasonal H3N2 Detected in Swine

 

#18,244

Last week, in two separate blogs (see here and here) we looked at the recent spillover of swine variant H3N2v from pigs to humans in two states (Colorado & Michigan).  

Since 2010 we've seen more than 500 scattered reports of infection with swine variant influenza viruses (H1N1v, H1N2v & H3N2v) around the nation, often associated with agricultural exhibits at county and state fairs. 

This cross-species sharing of influenza viruses is a two-way street, as humans have also transmitted human seasonal flu viruses to pigs (aka `reverse zoonosis'), where they may reassort with swine and (potentially) other novel influenza A viruses.

We saw this in 2016, when 18 human cases of swine variant H3N2v were identified across 2 states (Michigan & Ohio), 16 of which were caused by a reassorted virus, one with an H3 HA gene not previously seen in swine.

A 2016 MMWR: Investigation Into H3N2v Outbreak In Ohio & Michigan - found this HA gene was from human seasonal H3N2, writing:

The HA gene was likely introduced from humans into swine in 2010 or 2011, and viruses with this gene have circulated and evolved in swine to be genetically and antigenically different from both previous and currently circulating human seasonal influenza A(H3N2) viruses.  

Earlier this week the journal Nature published a report on multiple detections of the recent (2022-2023) H3N2 human seasonal flu virus circulating in pigs, a result of reverse zoonosis.  

This type of spillover is a concern since it not only poses a risk to swine production, it could also lead to the emergence of new (and potentially more dangerous) swine variant viruses. 

Due to its length, I've only included the link, abstract, and a few excerpts from the report.  Follow the link to read it in its entirety. I'll have a bit more after the break.

Article
 
Published: 13 August 2024
Reverse zoonosis of the 2022–2023 human seasonal H3N2 detected in swine

Michael A. Zeller, Daniel Carnevale de Almeida Moraes, Giovana Ciacci Zanella, Carine K. Souza, Tavis K. Anderson, Amy L. Baker & Phillip C. Gauger

npj Viruses volume 2, Article number: 27 (2024) Cite this article

Abstract

The Iowa State University Veterinary Diagnostic Laboratory detected nineteen human-to-swine reverse zoonoses of the 2022–2023 human seasonal H3N2 between November 2022 and November 2023. Cases from seven U.S. locations were detected: 3 Colorado, 1 Illinois, 1 Indiana, 2 Missouri, 7 North Carolina, 1 Ohio, and 1 Pennsylvania. One additional case was detected in Mexico and two cases were identified from Chile. Case samples were comprised of 4 nasal swabs and 15 oral fluids. Virus was successfully isolated from two of four nasal swab samples, but isolation from oral fluids was unsuccessful.

The swine detections of H3 human viruses were classified to one of two human-seasonal H3 clades, 3C.2a1b.2a.2b and 3C.2a1b.2a.2a.1. Phylogenetic inference indicated at minimum 7 reverse zoonotic events occurred, with possible swine-to-swine transmission following the initial spillover. Twelve neuraminidase genes were sequenced, and nine were classified as human-seasonal H3N2 lineage: the remaining were endemic swine IAV NA genes from the N2.2002B, N2.1998, or the N1.Classical lineage, suggesting reassortment. The two viral isolates obtained from nasal swab samples were sequenced and were entirely human-lineage viruses. 

Seven swine samples with human seasonal H3 were sequenced and revealed co-detections with H1 1A.3.3.3 (gamma), with internal gene segments from both the triple reassortant internal gene (TRIG) and pandemic 2009 lineages. Serologic investigation of samples from swine production systems provided evidence for infection with human seasonal H3N2. One farm in the United States and four farms in Mexico had concurrent virologic evidence. The swine-isolated 3C.2a1b.2a.2b H3N2 was antigenically distinct from endemic 1990.4.A, 2010.1, and 2010.2 swine H3N2 lineages, but retained antigenic similarity to a recent human seasonal H3N2 (A/Darwin/6/2021).

Pigs experimentally inoculated with a representative isolate demonstrated replication in the nose and lungs and minimal to mild macroscopic and microscopic lung lesions, but primary pigs did not transmit the virus to indirect contacts. If sustained in the pig population, this human seasonal H3 would represent the first new lineage detected in pigs the 2020 decade and present an emerging threat to swine health and production.

          (SNIP)

Discussion

During the 2022–2023 human influenza season, repeated H3 reverse zoonotic spillovers from humans into swine were detected. While human-to-swine transmission events were detected in the past through routine sampling by the ISU VDL, the number of independent introductions and overall detections during a single human influenza season is the highest recorded to date.

The detected viruses were from two phylogenetic clades estimated to have diverged in mid-2020 in humans, emphasizing that multiple spillover events occurred and that genetically diverse IAV were introduced into swine. HI titers detected against the human-like swine isolate from the human seasonal H3 2b clade and human seasonal H3 2a.1 clade virus indicate these strains were antigenically novel in swine and would further diversify the antigenic landscape if they became endemic.

(SNIP)

This study indicates an immediate potential threat to swine herd health with the introduction of an antigenically novel lineage of H3 IAV from humans. This study also underscores a reoccurring pattern of new introductions of human lineage IAV into swine, dictated by what is predominately circulating in humans2,5,14,47. 

The current best practice to prevent human-seasonal IAV introductions into swine herds are to adhere to stringent biosecurity protocols and to avoid letting ill humans interact with swine herds. Routine vaccination of swine has been shown to reduce viral shedding in swine56,57. Additionally, vaccination has been shown to reduce the chance of a reassortment event occurring, speculatively through the reduction in the number of days for a productive infection58. 

There is an inextricable link between IAV circulating in humans and swine. To break this pattern and mitigate future disease introduction additional focus will be needed to minimize spread of disease at the human-swine interface.

          (Continue . . . )

Reverse zoonosis isn't limited to pigs, or even influenza A. 

• We've seen repeated spillovers of SARS-CoV-2 into scores of non-human hosts (see Nature: Comparative Susceptibility of SARS-CoV-2, SARS-CoV, and MERS-CoV Across Mammals)

• Seasonal influenza infection of household pets (see I&ORD: Evidence of Reverse Zoonotic Transmission of Human Seasonal Influenza A Virus (H1N1, H3N2) Among Cats), farmed mink, and even marine mammals (see The 2009 H1N1 Virus Expands Its Host Range (Again))

• And even the spillover of Mpox from humans to other species (see Brazil MOH Reports A Monkeypox Infection In A Companion Animal (Dog)).

In order to try to reduce the risks, swine and poultry producers are often asked to get the seasonal flu vaccine, and there will be a push this fall to extend that to dairy workers as well (see CDC: $5 Million Initiative to Improve Uptake of Seasonal Flu Shots For Livestock Workers).

For some additional blogs on reverse zoonosis, you may with to revisit:

EID Journal: Human-to-Animal Transmission of SARS-CoV-2, South Korea, 2021

WHO/FAO/OIE Joint Statement On Monitoring SARS-CoV-2 In Wildlife & Preventing Formation of Reservoirs

WOAH: How Monkeypox Could Spill Back To Animals From Humans

Virology J: Human-like H3N2 Influenza Viruses In Dogs - Guangxi, China