# 8060
If you follow influenza topics closely, you may know that when influenza viruses gain antiviral resistance they often (but not always) take a performance hit when it comes to transmissibility. Back in 2007, it was widely held that the mutation that made the virus resistant to Tamiflu ® (H274Y), also reduced its biological fitness – suggesting that mutated versions of the viruses were unlikely to spread widely.
That notion was turned on its head when, a year later, the (old) seasonal H1N1 virus acquired resistance to oseltamivir, `broke with convention’ and spread like wildfire around the globe.
Fortunately, that highly resistant strain is no more, having been supplanted by the 2009 H1N1 pandemic virus. And resistant strains of the other two `human’ flu strains (H1N109 and H3N2) have failed to make much of an impact.
But earlier this year we saw signs that at least some of the isolates collected from patients infected with the H7N9 virus in China were resistant to antiviral medications (see EID Journal: R292K Substitution & Antiviral Resistance & mBio: Antiviral Resistance In H7N9). Most of these mutations appear to have developed after the patient was placed on antiviral meds.
Unlike the H1N1 and H3N2 resistant strains – which picks up resistance from the H274Y (Histidine to Tyrosine at neuraminidase position 275) – H7N9 resistant strains have the R292K Substitution (Arginine to Lysine at position 292 in the NA) – also known as Arg292Lys
Since we’ve no well documented human-to-human transmissions of this virus to look at, we really haven’t known if these resistant H7N9 strains – like their resistant H3N2 and 2009 H1N1 cousins – take a performance hit.
Today, in a report that appears in Nature Communications, we get evidence that suggests that resistant H7N9 viruses remain biologically `fit’ , competitive, and transmissible.
First a link to the Abstract (the full open access report is available at this link), then I’ll be back with a bit more.
Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility
Rong Hai, Mirco Schmolke, Victor H. Leyva-Grado, Rajagowthamee R. Thangavel, Irina Margine, Eric L. Jaffe, Florian Krammer, Alicia Solórzano, Adolfo García-Sastre, Peter Palese & Nicole M. Bouvier
Without baseline human immunity to the emergent avian influenza A(H7N9) virus, neuraminidase inhibitors are vital for controlling viral replication in severe infections. An amino acid change in the viral neuraminidase associated with drug resistance, NA-R292K (N2 numbering), has been found in some H7N9 clinical isolates. Here we assess the impact of the NA-R292K substitution on antiviral sensitivity and viral replication, pathogenicity and transmissibility of H7N9 viruses. Our data indicate that an H7N9 isolate encoding the NA-R292K substitution is highly resistant to oseltamivir and peramivir and partially resistant to zanamivir.
Furthermore, H7N9 reassortants with and without the resistance mutation demonstrate comparable viral replication in primary human respiratory cells, virulence in mice and transmissibility in guinea pigs. Thus, in stark contrast to oseltamivir-resistant seasonal influenza A(H3N2) viruses, H7N9 virus replication and pathogenicity in these models are not substantially altered by the acquisition of high-level oseltamivir resistance due to the NA-R292K mutation.
We’ve seen conflicting views on this virus’s pandemic potential (see TSRI: H7N9 Virus Still Binds Preferentially to Avian Receptors vs. Lancet: Tropism Of H7N9 In the Human Respiratory Tract vs.Nature: H7N9 Pathogenesis and Transmissibility In Ferrets & Mice ) over the summer and fall.
The good news is that we’ve not seen any evidence that any of the H7N9 viruses to date are capable of efficiently transmitting among humans.
That could change, of course. But no one really knows how many adaptations are needed for this virus to become a pandemic contender. Since human immunity to the H7N9 virus is likely to be minimal, and this virus is capable of producing significant morbidity and mortality, today’s findings are clearly important and a bit worrisome.
But none of this increases the odds that the H7N9 virus will spark a pandemic.
It does suggest, however, that our pharmacological options for treating it could be limited, should that ever happen.
