Frequent reassortment among influenza C viruses

Abstract

In a 9-year survey from December 1990 to December 1999 in Sendai City, Japan, we succeeded in isolating a total of 45 strains of influenza C virus. These 45 strains were isolated in clusters within 4 months in a year, especially from winter to early summer. Previous studies of the hemagglutinin-esterase genes of various influenza C virus isolates revealed the existence of five distinct virus lineages (Aichi/1/81-, Yamagata/26/81-, Mississippi/80-, Sao Paulo/82-, and Kanagawa/1/76-related lineage) in Japan between 1970 and the early 1990s (Y. Matsuzaki, K. Mizuta, H. Kimura, K. Sugawara, E. Tsuchiya, H. Suzuki, S. Hongo, and K. Nakamura, J. Gen. Virol. 81:1447-1452, 2000). Antigenic and genetic analyses of the 45 strains showed that they could be divided into these five virus lineages and a few antigenic groups were cocirculating in Sendai City. In 1990 and 1991 the dominant antigenic group was the Aichi/1/81 virus group, and in 1992 it was Yamagata/26/81 virus group. The Mississippi/80 virus group was isolated from 1993 to 1996, and the Yamagata/26/81 virus group reemerged in 1996 and continued to circulate until 1999. This finding led us to a speculation that the replacement of the dominant antigenic groups had occurred by immune selection within the human population in the restricted area. Phylogenetic analysis of seven RNA segments showed that 44 viruses among the 45 strains isolated in our surveillance work were reassortant viruses that have various genome compositions distinguishable from those of the reference strains of the each lineage. This observation suggests that the reassortment between two different influenza C virus strains occurs frequently in nature and the genome composition of influenza C viruses may influence their ability to spread in humans.

FIG. 1.

Monthly distribution and antigenicity of influenza C virus strains isolated in Sendai City between December 1990 and December 1999.

FIG. 2.

Phylogenetic tree of influenza C virus HE genes. The region from nucleotides 64 to 1989 was used for analysis. The Sendai isolates (those listed in Table 2 and MI391) with HE antigenicities identical to those of AI181, YA2681, MS80, SP82, and KA176 are marked (∗, †, ‡, §, and ¶, respectively). Horizontal distances are proportional to the minimum number of nucleotide differences needed to join the gene sequences. Numbers below or above the branches are the bootstrap probabilities (percentages) of each branch as determined by the PHYLIP program (version 3.573c).

FIG. 3.

Phylogenetic trees for the PB2 (A), PB1 (B), P3 (C), NP (D), M (E,) and NS (F) genes of influenza C virus isolates. The nucleotide sequences of the following regions were used for analysis: nucleotides 52 to 520 for the PB2 gene, nucleotides 50 to 425 for the PB1 gene, nucleotides 49 to 420 for P3 genes, nucleotides 71 to 670 for the NP gene, nucleotides 26 to 1,147 for the M gene, and nucleotides 28 to 889 for the NS gene. The Sendai isolates listed in Table 2, having the HE genes of the AI181-, YA2681-, MS80-, SP82-, and KA176-related lineages, are marked (∗, †, ‡, §, and ¶, respectively). Horizontal distances are proportional to the minimum number of nucleotide differences needed to join the gene sequences. Numbers below or above the branches are the bootstrap probabilities (percentages) of each branch as determined by the PHYLIP program (version 3.573c).

FIG. 3.

Phylogenetic trees for the PB2 (A), PB1 (B), P3 (C), NP (D), M (E,) and NS (F) genes of influenza C virus isolates. The nucleotide sequences of the following regions were used for analysis: nucleotides 52 to 520 for the PB2 gene, nucleotides 50 to 425 for the PB1 gene, nucleotides 49 to 420 for P3 genes, nucleotides 71 to 670 for the NP gene, nucleotides 26 to 1,147 for the M gene, and nucleotides 28 to 889 for the NS gene. The Sendai isolates listed in Table 2, having the HE genes of the AI181-, YA2681-, MS80-, SP82-, and KA176-related lineages, are marked (∗, †, ‡, §, and ¶, respectively). Horizontal distances are proportional to the minimum number of nucleotide differences needed to join the gene sequences. Numbers below or above the branches are the bootstrap probabilities (percentages) of each branch as determined by the PHYLIP program (version 3.573c).

FIG. 3.

Phylogenetic trees for the PB2 (A), PB1 (B), P3 (C), NP (D), M (E,) and NS (F) genes of influenza C virus isolates. The nucleotide sequences of the following regions were used for analysis: nucleotides 52 to 520 for the PB2 gene, nucleotides 50 to 425 for the PB1 gene, nucleotides 49 to 420 for P3 genes, nucleotides 71 to 670 for the NP gene, nucleotides 26 to 1,147 for the M gene, and nucleotides 28 to 889 for the NS gene. The Sendai isolates listed in Table 2, having the HE genes of the AI181-, YA2681-, MS80-, SP82-, and KA176-related lineages, are marked (∗, †, ‡, §, and ¶, respectively). Horizontal distances are proportional to the minimum number of nucleotide differences needed to join the gene sequences. Numbers below or above the branches are the bootstrap probabilities (percentages) of each branch as determined by the PHYLIP program (version 3.573c).

FIG. 4.

Deduced pattern for gene reassortment among the Sendai isolates of influenza C virus having the HE genes of the AI181-, YA2681-, MS80-, and KA176-related lineage.