Influenza evolution is propelled via two distinct mechanisms; antigenic drift and antigenic shift.
Antigenic drift causes small, incremental changes in the virus over time. Drift is the standard evolutionary process of influenza viruses, and often comes about due to replication errors that are common with single-strand RNA viruses (see NIAID Video: Antigenic Drift).
Shift occurs when one virus swap out chunks of their genetic code with gene segments from another virus in a co-infected host. This is known as reassortment (see graphic above).
While far less common than drift, shift can produce abrupt, dramatic, and sometimes pandemic inducing changes to the virus (see NIAID Video: How Influenza Pandemics Occur).
We worry most about reassortment occurring in birds and swine, since both are susceptible to a wide range of flu viruses. But many other species - including humans - are potentially capable of producing reassorted viruses.
Up until 2009, human co-infection with influenza A had only rarely been reported. Duel infections have been noted, but usually with an `A’ and a `B’ virus.
In 2008, we saw a report of an Indonesian teenager who tested positive both H5N1 and the seasonal flu strain H3N2 (see CIDRAP report Avian, human flu coinfection reported in Indonesian teen), demonstrating that co-infection with Influenza A was possible.
But the big breakthrough came in 2009 when the pandemic H1N1 virus emerged and co-circulated for a time with the old seasonal H1N1 virus, allowing scientists in New Zealand to isolate and document 11 cases of Influenza A co-infection (see EID Journal: Co-Infection By Influenza Strains for the full story).
While reassortant viruses were not reported at that time, the authors wrote:
Co-infection with seasonal influenza A (H1N1) and pandemic (H1N1) 2009 could result in reassortant viruses that may acquire new characteristics of transmission, virulence, and oseltamivir susceptibility. Results from oseltamivir-sensitivity testing on viral culture suggested the possibility of co-infections with oseltamivir-resistant (seasonal A [H1N1]) and -susceptible (pandemic [H1N1] 2009) viruses.
Today, many of those same researchers are back with a new analysis of those 11 co-infected patients, and evidence that multiple reassortant viruses were produced.
First the abstract, and link to the study, after which I'll have more.
Pandemic-seasonal H1N1 reassortants recovered from patient material display a phenotype similar to the seasonal parent.
ABSTRACTWe have previously shown that eleven patients became naturally co-infected with seasonal H1N1 (A/H1N1) and pandemic H1N1 (pdm/H1N1) during the Southern hemisphere winter of 2009 in New Zealand.Reassortment of influenza A viruses is readily observed during co-infection of host animals and in vitro, however, reports of reassortment occurring naturally in humans are rare. Using clinical specimen material, we show reassortment between the two co-infecting viruses occurred with high likelihood directly in one of the previously identified patients.Despite the lack of spread of these reassortants in the community, we did not find them to be attenuated in several model systems for viral replication and virus transmission: multistep growth curves in differentiated human bronchial epithelial cells revealed no growth deficiency in six recovered reassortants when compared to A/H1N1 and pdm/H1N1 isolates.Two reassortant viruses were assessed in ferrets and showed transmission to aerosol contacts. This study demonstrates that influenza virus reassortants can arise in naturally co-infected patients.IMPORTANCE Reassortment of influenza A viruses is an important driver of virus evolution, but little has been done to address humans as hosts for the generation of novel influenza viruses. We show here that multiple reassortant viruses were generated during natural co-infection of a patient with pandemic H1N1 (2009) and seasonal H1N1 influenza A viruses.Though apparently fit in model systems, these reassortants did not become established in the wider population, presumably due to herd immunity against their seasonal H1 antigen.
Since 2009, with increased surveillance and better tools, we've seen a growing number of reports of human co-infection with influenza A:
But evidence of the generation of `biologically fit' reassortant viruses from a human co-infection have been less common.
- However, last November, in J Clin Virol: Influenza Co-Infection Leading To A Reassortant Virus, we looked at co-infection in a Cambodian patient with both seasonal H3N2 and H1N1pdm09 which led to a new, reassortant H3N2 virus.
- And in 2011 we saw a similar co-infection in a 16 month old boy in Canada that led to the creation of a unique hybrid reassorted virus (see Webinar: pH1N1 – H3N2 A Novel Influenza Reassortment).
And as the number of novel viruses (avian, swine variant, and others) making brief forays into the human population increases, so does the likelihood of seeing human co-infections with seasonal flu viruses.
While undoubtedly a rare occurrence, with an even lower likelihood of producing a new, easily transmittable reassortant virus – the risk is not zero and the potential impact could be huge – as Hong Kong’s CHP Director Dr. Ko Wing-man warns almost every year.
Which is why we pay so much attention whenever we see novel flu viruses - even mild ones like H9N2 or H3N2v - making the leap to humans.