Emergence of influenza A(H1N1)pdm09 genogroup 6B and drug resistant virus, India, January to May 2015

Abstract

To investigate the aetiology of the 2015 A(H1N1)pdm09 influenza outbreak in India, 1,083 nasopharyngeal swabs from suspect patients were screened for influenza A(H1N1)pdm09 in the state of Madhya Pradesh. Of 412 positive specimens, six were further characterised by phylogenetic analysis of haemagglutinin (HA) sequences revealing that they belonged to genogroup 6B. A new mutation (E164G) was observed in HA2 of two sequences. Neuraminidase genes in two of 12 isolates from fatal cases on prior oseltamivir treatment harboured the H275Y mutation.An epidemic of influenza A(H1N1)pdm09, affecting over 39,000 persons and causing more than 2,500 deaths occurred in India in 2015 [1]. We show that genotype 6B strains forming two sub-lineages circulated during the outbreak. Comparison of the sequences of six outbreak strains recovered in this work, to other published genotype 6B sequences, also reveals a unique combination of previously-reported mutations in the haemagglutinin (HA) gene. Two of the six sequences additionally display a E164G mutation in HA2, which has not been reported to date, moreover a N129D mutation in HA1 is observed for two sequences derived from patients with severe disease. Among strains analysed from 12 fatal cases on prior oseltamivir treatment, two harbour the H275Y mutation in the neuraminidase (NA) gene, which confers resistance to this antiviral.

Predominance of influenza A(H1N1)pdm09 virus genetic subclade 6B.1 and influenza B/Victoria lineage viruses at the start of the 2015/16 influenza season in Europe

“…For 150 viruses, reported in strain-based manner, both genetic and antigenic data were available. Analysis of A(H1N1)pdm09 HA gene sequences from 12 countries (Czech Republic, Finland, Greece, Ireland, Netherlands, Norway, Portugal, Romania, Russia, Slovenia, Spain and Sweden) reported to TESSy, with provision of accession numbers in publicly accessible databases, confirmed that all these analysed viruses possessed the signature amino acid variations that define subgroup 6B viruses: D97N, K163Q, S185T, K283E and A256T [7][8][9]. All 215 analysed sequences, apart from two viruses isolated in Russia, also carried P83S and I321V substitutions in HA1.…”

“…Noteworthy, 80% of the analysed HA sequences have gained a potential glycosylation site S162N. No D222G/E/N substitutions were detected, nor N129D which was recently identified in India in two severe or fatal cases [9]. If the emerging groups continue to diversify from the vaccine component, their antigenic properties may change and the vaccine effectiveness might be reduced.…”

“…In Europe, within the detected A subtypes, influenza A(H1N1) pdm09 predominated during 2010/11, 2012/13 and 2013/14 seasons and concerned 97% [11], 62% [12] and 53% [13] of subtyped influenza viruses respectively, with variation in country-specific proportions. The [1,8,9]. This subgroup appeared in 2012/13 and became predominant in 2013/14 [14].…”

Genetic Characterization of Circulating 2015 A(H1N1)pdm09 Influenza Viruses from Eastern India

“…It was proposed that these mutations may have caused the disease severity of 2015 outbreak [11]. Recently, another study from central India reported a new mutation E164G in HA2 sequences [12]. …”

Severe and Fatal Influenza Cases in Russia in 2014-2015

“…In 2014-2015, A(H1N1pdm09) activity was variable with notable widespread outbreaks in the Indian subcontinent and in parts of Africa (Parida et al, 2016;Takashita et al, 2016). The phylogenetic tree for the HA gene of H1N1pdm09 viruses can be divided into nine major genetic groups, although recently isolated viruses belong to group 6.…”