Cluster of Oseltamivir-Resistant and Hemagglutinin Antigenically Drifted Influenza A(H1N1)pdm09 Viruses, Texas, USA, January 2020

Abstract

Four cases of oseltamivir-resistant influenza A(H1N1)pdm09 virus infection were detected among inhabitants of a border detention center in Texas, USA. Hemagglutinin of these viruses belongs to 6B.1A5A-156K subclade, which may enable viral escape from preexisting immunity. Our finding highlights the necessity to monitor both drug resistance and antigenic drift of circulating viruses.

Keywords: Texas; United States; antigenic drift; antimicrobial resistance; drug resistance; influenza; influenza A(H1N1); neuraminidase inhibitor; transmission; viruses.

Figure 1

Evolutionary relationships of the HA (A) and NA (B) genes of influenza A(H1N1)pdm09 viruses circulating in the United States during the 2019–20 influenza season compared with reference viruses. We generated phylogenetic trees using MEGA software version 10.1.8 (http://www.megasoftware.net) and the bootstrap method (1,000 replications). We computed evolutionary distances by using the maximum composite likelihood model. Analysis included 40 representative A(H1N1)pdm09 HA and NA gene sequences. Boldface indicates oseltamivir-resistant viruses carrying NA-H275Y substitution; asterisks indicate vaccine viruses. A/California/07/2009 virus (the first A(H1N1)pdm09 vaccine) is used as a reference for ancestry (root) and numbering. Scale bar represents nucleotide substitutions per site. HA, hemagglutinin; NA, neuraminidase.

Figure 2

In vitro replicative fitness of influenza A(H1N1)pdm09 cluster and control viruses. The growth kinetics of the 2 viruses, the cluster virus A/Texas/137/2020, and A/New York/19/2020, were assessed using MDCK (A) and hCK (B) cell lines. These viruses have identical HA and NA amino acid sequences, except the H275Y substitution in NA. Cell monolayers were infected at a multiplicity of infection of 0.002 and the supernatants were harvested at 8, 12, 24, 48, and 72 hours postinoculation. Infectious virus titers were determined and expressed as log₁₀ TCID₅₀/mL. The lower limit of virus detection is 1.75 log₁₀ TCID₅₀/mL. Data are shown as mean +SD; we used the unpaired t-test with Welch’s correction for statistical comparisons (asterisk indicates p˂0.05). The hCK cell line was kindly provided by Dr. Y. Kawaoka (University of Wisconsin, Madison, WI, USA) per material transfer agreement. HA, hemagglutinin; hCK, humanized MDCK cells; NA, neuraminidase; TCID₅₀, median tissue culture infectious dose.