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. 2009 Aug;47(8):2475-82.
doi: 10.1128/JCM.00115-09. Epub 2009 Jun 24.

Emerging genotypes of human respiratory syncytial virus subgroup A among patients in Japan

Yugo Shobugawa  1 , Reiko Saito, Yasuko Sano, Hassan Zaraket, Yasushi Suzuki, Akihiko Kumaki, Isolde Dapat, Taeko Oguma, Masahiro Yamaguchi, Hiroshi Suzuki
Affiliations

Emerging genotypes of human respiratory syncytial virus subgroup A among patients in Japan

Yugo Shobugawa et al. J Clin Microbiol. 2009 Aug.

Abstract

Human respiratory syncytial virus (HRSV) is a common etiological agent of acute lower respiratory tract disease in infants. We report the molecular epidemiology of HRSV in Niigata, Japan, over six successive seasons (from 2001 to 2007) and the emerging genotypes of HRSV subgroup A (HRSV-A) strains. A total of 488 HRSV samples were obtained from 1,103 screened cases in a pediatric clinic in Niigata. According to the phylogenetic analysis, among the PCR-positive samples, 338 HRSV-A strains clustered into the previously reported genotypes GA5 and GA7 and two novel genotypes, NA1 and NA2, which were genetically close to GA2 strains. One hundred fifty HRSV-B strains clustered into three genotypes, namely, GB3, SAB3, and BA, which has a 60-nucleotide insertion in the second hypervariable region of the G protein. The NA1 strains emerged first, in the 2004-2005 season, and subsequently, the NA2 strain emerged in the 2005-2006 season. Both strains caused large epidemics in the 2005-2006 and 2006-2007 seasons. The average age of children who were infected with NA2 strains was significantly higher than that of those infected with GA5 and the frequency of reinfection by NA2 was the highest among all genotypes, suggesting that this genotype possessed new antigenicity for evading past host immunity. This is the first paper to show a possible correlation between an emerging genotype, NA2, and large outbreaks of HRSV in Japan. Continuing studies to follow up the genetic changes and to clarify the mechanism of reinfection in HRSV are important steps to understand HRSV infections.

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Figures

FIG. 1.
FIG. 1.
Comparison of monthly number of HRSV cases between a hospital-based survey in Niigata and national surveillance in Japan. The monthly distribution of numbers of screened cases in hospital-based surveillance of HRSV in Niigata City is shown by the stacked bar graph; closed boxes indicate numbers of PCR-positive samples, and open boxes denote PCR-negative samples. The numbers of cases in national surveillance of HRSV in Japan are shown by the line graph.
FIG. 2.
FIG. 2.
Phylogenetic trees for HRSV-A (a) and HRSV-B (b) nucleotide sequences based on the second variable region of the G protein (270 or 330 bp) using the neighbor-joining method with MEGA, version 4. Genotypes were assigned by Peret et al. (genotypes GA1 to GA7 and GB1 to GB4) (27) and Venter et al. (genotypes SAA1 and SAB1 to SAB3) (37). The new type, named BA virus, comprises strains with a 60-nucleotide insertion. Reference GenBank sequences of strains from throughout the world were compared with strains from Niigata (NG); the comparison strains were from Rochester, NY (CH) (27); Winnipeg, Manitoba, Canada (CN) (26); Houston, TX (TX) (26); Rochester, NY (NY) (26); St. Louis, MO (MO) (26); Soweto, South Africa (SA) (37); Birmingham, AL (AL) (26); West Virginia (WV) (32); Sapporo, Japan (SAP) (22); and Buenos Aires, Argentina (BA) (35). The scale bars show the proportions of nucleotide substitutions, and the numbers at the branches are bootstrap values determined for 1,000 iterations. Only bootstrap values of greater than 70% significance are shown.
FIG. 3.
FIG. 3.
Deduced amino acid alignments of the second variable region of the G protein gene from HRSV-A (a) and HRSV-B (b) Niigata strains. Alignments are shown relative to the sequences of prototype strain A2 (GenBank accession number M11486) (16) and genotype BA strain BA4128/99B (GenBank accession number AY333364) (35). The amino acid numbering corresponds to strain A2 G protein positions 220 to 298 for the HRSV-A viruses and to strain BA4128/99B G protein positions 219 to 315 for the HRSV-B viruses. Identical residues are indicated by dots. Stop codons are indicated by asterisks. Potential N-glycosylation sites (NXT, where X is not a proline) are indicated by gray shading. In panel a, second N-glycosylation sites (aa 250) are indicated by rectangles and third sites (aa 251) by dotted rectangles. In panel b, the two copies of the duplicated 20-amino-acid region in HRSV-B viruses are indicated by rectangles.
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