Adamantane-Resistant Influenza A Viruses in the World (1902–2013): Frequency and Distribution of M2 Gene Mutations

<div><p>Adamantanes (amantadine and rimantadine) have been used to prevent and treat influenza A virus infections for many years; however, resistance to these drugs has been widely reported in the world. To investigate the frequency and distribution of M2 gene mutations in adamantane-resistant influenza variants circulated in the world between 1902 and 2013, 31251 available M2 protein sequences from different HA-subtype influenza A viruses (H1–H17) were analyzed and adamantane resistance-associated mutations were compared (L26F, V27A, A30T, A30V, S31N, G34E, and L38F). We find that 45.2% (n = 14132) of influenza A (H1–H17) viruses circulating globally were resistant to adamantanes, and the vast majority of resistant viruses (95%) bear S31N mutations. Whereas, only about 1% have V27A mutations and other mutations (L26F, A30T, G34E, and L38F) were extremely rare (their prevalence appeared to be < 0.2%). Our results confirm that H1, H3, H5, H7, H9, and H17 subtype influenza A viruses exhibit high-level resistance to adamantanes. In contrast, the appearance of adamantane-resistant mutants in H2, H4, H6, H10, and H11 subtypes was rare. However, no adamantane resistance viruses were identified among other HA subtypes (H8, H12–H16). Our findings indicate that the frequency and distribution of adamantane-resistant influenza variants varied among different HA subtypes, host species, years of isolation, and geographical areas. This comprehensive study raises concerns about the increasing prevalence of adamantane-resistant influenza A viruses and highlights the importance of monitoring the emergence and worldwide spread of adamantane-resistant variants.</p></div

Additional file 3: of Detection and genetic characterization of feline bocavirus in Northeast China

A maximum-likelihood phylogenetic tree based on partial NS1 gene (705 nt) of feline bocavirus. The black triangles indicate strains belonging to FBoV-1 identified in this study, and the black squares indicate strains belonging to FBoV-2 identified in the present study. (TIF 635 kb

Additional file 2: of Detection and genetic characterization of feline bocavirus in Northeast China

Summary of detailed clinical informations for the 51 FBoV-positive samples identified in the present study. M, male; FM, female; PVC, private veterinary clinic; ASC, animal shelter center. (DOC 98 kb

Additional file 4: of Detection and genetic characterization of feline bocavirus in Northeast China

Comparison of nucleotide and amino acid sequence identity in the complete genome and three ORFs of different feline bocavirus genotypes. Nucleotide similarity (%)/ deduced amino acid similarity (%) is shown in the table. Six strains identified in this study were compared to each other and were compared with other reference strains of different FBoV genotypes based on the complete genome and three ORFs. Bold text indicates that the similarity between identified strains and reference strains is higher than 85%. (DOC 62 kb

Additional file 5: of Detection and genetic characterization of feline bocavirus in Northeast China

Phylogenetic tree based on the complete genome of bocaviruses. The phylogenetic analysis was performed using maximum-likelihood method in MEGA 7.0 software. The black triangles and black squares indicate FBoV-1 strains and FBoV-2 strains, respectively, identified in this study. (TIF 1023 kb

Additional file 1: of Detection and genetic characterization of feline bocavirus in Northeast China

List of representative bocavirus strains obtained from the GenBank database for genetic analysis and phylogenetic tree construction. (DOC 64 kb

The frequencies of adamantane-resistant variants among all influenza A (H1-H17) viruses used in this study.

<p>^a adamantane resistance-associated mutations present in the M2 Protein of viruses were at positions L26F, V27A, A30T, A30V, S31N, G34E, and L38F that confer resistance to adamantanes.</p><p>^b Appearance time to adamantane resistant variants.</p><p>^c The frequency of adamantane resistant variants among different HA subtypes.</p><p>The frequencies of adamantane-resistant variants among all influenza A (H1-H17) viruses used in this study.</p