The pandemic H3N2 virus strain is a descendant of the H2N2 strain (thus still maintaining 5 gene segments of the Spanish flu 1918 H1N1 virus lineage) by another round of gene segment replacements encoding PB1 and HA protein from a distinct avian influenza virus.

The year was 1957 and the disease was the Asian flu in what some called the H2N2 pandemic. The H2N2 virus was made up of three genes originating from the avian influenza A virus, according to the.

In 1968 the H2N2 Asian influenza virus was completely replaced by an H3N2 virus and this virus was also a reassortment between avian and human viruses. This virus was moderate in its pathogenicity (in U.S. 33,800 excess mortality) but the attack rate (40%) was highest in 10–14 year olds.