Thursday, May 19, 2016

Genomic Characteristics Of 2 A(H9N2) Virus Isolates From Humans In Anhui Province - 2015


Although they don't tend to get quite as much attention as their HPAI cousins, primarily because they usually pose little immediate threat to poultry or human health, low path (LPAI) avian influenza viruses are important for a number of reasons:

  1. LPAI viruses - particularly H5 and H7 subtypes - can sometimes quickly evolve into HPAI viruses ( see JVI  Emergence of a Highly Pathogenic Avian Influenza Virus from a Low Pathogenic Progenitor).
  2. While rare, we've seen at least one LPAI virus (H7N9) turn out to be highly pathogenic in humans
  3. And LPAI viruses are continually reassorting with both LPAI and HPAI viruses - helping to create new, hybrid viruses. 

In this last category, few avian viruses can match the promiscuity of LPAI H9N2.  In recent years H9N2 has shared its internal genes with - and thereby helped to create - some of the most worrisome avian flu viruses (H5N1, H7N9, H10N8, H5N8, etc.) on the planet.

In the past, we’ve looked at this propensity of the H9N2 virus to reassort with other avian flu viruses (see PNAS: Reassortment Of H1N1 And H9N2 Avian viruses & PNAS: Reassortment Potential Of Avian H9N2), and these studies have shown the H9N2 quite capable of producing `biologically fit’ and highly pathogenic reassortant viruses.

In a similar vein, in early 2014  The Lancet carried a report entitled Poultry carrying H9N2 act as incubators for novel human avian influenza viruses.

But risks from H9N2 go beyond facilitating the creation of viable reassorted subtypes.  The H9N2 virus can infect humans (and other mammals) on its own - and while it generally produces a mild illness - we've seen a recent escalation in the number of cases reported around the world.

In the 16 years between 1998 and the end of 2014, the WHO had been notified of just 18 cases globally (see FluTrackers Global Cumulative H9N2 Partial Case List 1998-2016).  Over the last 16 months, however, the WHO has been notified of 11 new cases (5 in China,  4 in Egypt, and 2 in Bangladesh). 

All of which raises the question.  Are we just getting better at detecting human infections, or is the virus getting better at infecting humans?

The argument for better surveillance is a strong one, since China and Egypt both endure yearly avian flu epidemics, and have both significantly increased routine testing of hospitalized flu patients for a variety of novel viruses. 

Quite simply, the more you look, the more you are likely to find.

And while this increased surveillance could easily explain this  jump in cases, at the same time we've been watching the continual evolution of  H9N2, and indications are the virus continues to acquire mammalian adaptations. 

All of which brings us to a new report, from the CMA Journal (in Chinese), that examined the genetic characteristics of two 2015 H9N2 infections in Anhui Province, and find that H9N2 continues to evolve and adapt.

Genomic characteristics of 2 strains of influenza A(H9N2)virus isolated from human infection cases in Anhui province.
[Article in Chinese]


To understand genomic characteristics of 2 strains of influenza A(H9N2)virus isolated from human infection cases in Anhui province in 2015.
Two human infection with H9N2 virus were confirmed by national influenza surveillance laboratory network in Anhui through viral isolation in April and September, 2015, respectively. The full genomic sequences of the two viral isolates were analyzed in this study by using molecular bioinformatics software Mega 6.0.
Human infection with H9N2 virus was first reported in Anhui province. The analysis of genomic sequence showed that the HA and NA genes of the two H9N2 isolates belonged to A/Chicken/Shanghai/F/98(H9N2)-like lineage, and shared high identity with H9N2 virus circulating in poultry in 2013. 

The PB2 and MP genes belonged to the A/quail/Hong Kong/G1/97-like lineage, and shared high homology with H7N9, H10N8 or H6N2 viruses. The amino acid sequence alignment results showed that several mutations for human infection tropism presented in the two virus strains, including Q226L, H183N and E190T in HA; S31N in M2; 63-65 deletion in NA. In addition, the H9N2 influenza virus strains possessed the PSRSSR\GL motif in HA. 

Meanwhile several human-like signatures, including PA-100A, PA-356R and PA-409N were also found in the two virus strains.
The H9N2 viruses isolated from human infection cases in Anhui province belonged to a reassortant virus originated from different lineage H9N2 avian influenza virus. The virus has possessed several human susceptibility locus.

Like many far-ranging avian flu viruses, the H9N2 genome varies by locale. The viruses you see in China differ from the versions you’ll find in Bangladesh, or the Middle East.

Over the past couple of years we've seen a lot of research on the diversity of H9N2, including:

While the H9N2 virus may have some limited pandemic potential on its own, the bigger danger is that it will acquire more `mammalian' adaptations, and then share those (via reassortment) with other, more pathogenic, viruses.

All of which makes H9N2 watching more than just an academic exercise.