Neuraminidase inhibitors susceptibility profiles of highly pathogenic influenza A (H5N1) viruses isolated from avian species in India (2006–2015).

Abstract We tested 65 highly pathogenic avian influenza (HPAI) A(H5N1) viruses, isolated from avian species in India between 2006 and 2015, for susceptibility to the FDA approved neuraminidase (NA) inhibitors (NAIs), oseltamivir and zanamivir using a phenotypic fluorescence-based assay. The overall incidence of resistant variants among HPAI A(H5N1) viruses was 7.69% (5/65). The NA inhibition assay identified 3 viruses resistant to oseltamivir (N294S substitution, N2 numbering) and 2 cross-resistant to oseltamivir and zanamivir (E119A or I117V+E119A substitutions), all of which belonged to hemagglutinin (HA) clade 2.2 (5/17) and predominantly circulated in Indian poultry during 2006–2010. In comparison to E119A substitution alone, viruses with I117V+E119A double substitutions showed greater reduction in susceptibility to both oseltamivir and zanamivir. The NAI resistance-associated NA markers, identified in this study, were as a result of naturally occurring mutations. Of note, 48 viruses of HA clade 2.3.2.1 that circulated in Indian poultry during 2011–2015 were susceptible to both oseltamivir and zanamivir. It is essential to monitor NAI susceptibility among human and avian HPAI A(H5N1) viruses that would provide baseline data to develop strategies for pandemic preparedness and therapeutic interventions. Highlights • The overall incidence of NAI–resistant variants among HPAI A(H5N1) viruses in India was 7.69% (5/65). • The NAI–resistant clade 2.2 viruses carried either single (E119A, N294S) or double (I117V+E119A) NA substitution(s). • The double (I117V+E119A) NA substitutions further reduced the susceptibility to NAIs compared to E119A substitution. • The HPAI A(H5N1) viruses of clade 2.3.2.1 that circulated in Indian poultry since 2011 were susceptible to NAIs. [ABSTRACT FROM AUTHOR]