G4 EA H1N1 is a strain of the H1N1 swine flu subtype of influenza A, which is a genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus. The strain was common on pig farms in China from 2016 to 2020. G4 EA H1N1 replicates efficiently in human airways and has infected people without causing disease. A 2020 study conducted by researchers at the Chinese Center for Disease Control and the China Agricultural University stated that this strain of G4 virus has characteristics that make is a candidate pandemic virus and recommended controlling spread in pigs and monitoring human populations.
Influenza viruses are members of the Orthomyxoviridae family of enveloped viruses which have a genome composed of segmented negative-sense single-strand RNA segments. There are four genera in this family, types A, B, C and Thogotovirus, with genera A and B clinically relevant for humans. H1N1 swine flu subtype of influenza A causes respiratory tract infections in the host with symptoms that include nasal secretions, chills, fever, decreased appetite and possibly lower respiratory tract disease. H1N1 is common in pigs worldwide and people closely associated with pigs may develop zoonotic swine flu. Through reassortment, the antigenic characteristics of the virus can change leading to human infection with H1N1. While person-to-person transmission is usually not efficient cases where H1N1 became efficient occurred in the influenza A pandemics of 1918, also known as the Spanish flu, and 2009. H1N1 stands for hemagglutinin type 1 and neuraminidase type 1, the two main surface antigens.
Segmented RNA viruses such as Influenza A undergo reassortment as an evolutionary mechanism with a role in virus emergence and interspecies transmission. When a host is infected with multiple RNA viruses there may be shuffling of gene segments to generate progeny viruses with novel genome combinations. Acquisition of genetic markers in the virus which overcome host barriers is quicker with reassortment compared to mutation alone.
The swine influenza ecosystem includes the classical swine (CS) lineage, the North American triple-reassortant (TR) lineage and the Eurasian avian-like (EA) lineage, which cocirculate in pigs. After the 2009 H1N1 pandemic, pdm/09 H1N1 spread back into pig herds around the world. G4 EA H1N1 contains 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes. Similar to the pdm/09 virus, which caused the 2009 H1N1 pandemic, G4 viruses bind to human-type receptors, produce higher progeny virus in human airway epithelial cells and are able to infect with aerosol transmission in ferrets. Preexisting population immunity will not provide protection against G4 reassortant EA H1N1 due to low cross-reactivity with human influenza vaccine strains.
G4 is similar to pdm/09 in that it preferentially binds human-like SAα2,6Gal receptor and effectively transmits in the ferret model. As of the June 2020, the general population who is not in contact with pigs lacked antibodies against G4 virus, but swine-exposed adults showed seroprevalence of 10.4%, 35/338, supporting the hypothesis of G4 transmission from pigs to humans but not from humans to humans. Controlling the prevalence of G4 EA H1N1 viruses in pigs and monitoring of human populations working with swine were recommended to prevent further human adaptation and decrease the risk of human pandemic.