Genetic analysis of an influenza B virus isolated from a patient with encephalopathy in Japan*

Abstract

An influenza B virus, B/Saga/S172/99 (SAG99), was isolated from the nasopharynx of a patient with encephalopathy/encephalitis in Japan in 1999. To clarify the molecular characteristics of this virus, detailed analysis of the gene segments coding for the hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), matrix protein (M) and non-structural protein (NS) was undertaken. All five genes of SAG99 showed high nucleotide and predicted amino acid similarities with those of recent non-encephalopathic strains isolated in the same epidemic season. Subsequent phylogenetic analysis revealed that all five gene segments of SAG99 analyzed in the present study were most similar to those of the recent Yamagata/16/88-like viruses. The hemagglutinin and neuraminidase proteins of SAG99 were each distinguished from those of recent epidemic strains by one characteristic amino acid substitution. These substitutions were not found in the previously reported encephalopathy/encephalitis-derived influenza B viruses, and we could not find any common characteristic amino acid changes in SAG99 and these viruses. Similarly, among the internal proteins studied, only the M2 protein of SAG99 was found to contain a single novel amino acid change when compared with other recent isolates. Thus, it was apparent that SAG99 contained very few amino acid differences when compared with other epidemic viruses. The association of recent B/Yamagata/16/88-like viruses with encephalitis/encephalopathy observed in the present study and previously suggest that these viruses may have a higher potential for causing neurological complications in certain individuals.

Genetic diversity of influenza B virus: The frequent reassortment and cocirculation of the genetically distinct reassortant viruses in a community

“…the following two seasons, Yamagata/222/2002, Yamagata/115/2003, Yamagata/1246, and Yamagata/ 1311, were also determined here. Phylogenetic trees of individual genes were constructed using these sequences in addition to the previous reported sequences [Yamashita et al, 1988;Kanegae et al, 1990;Rota et al, 1990;Nerome et al, 1998;Lindstrom et al, 1999;McCullers et al, 1999;Hiromoto et al, 2000;Shiraishi et al, 2001;Shaw et al, 2002]. The genome composition of the newly studied isolates is summarized in Table I. HA1 and NS gene trees.…”

Effect of mass immunization against influenza encephalopathy on mortality rates in children

“…[12][13][14][15][16][17][18][19][20][21] Some studies in Japan have provided direct evidence of the influenza virus genome in cerebrospinal fluid. [22][23][24] However, recent studies indicate that several cytokines might mediate the disease and a high plasma concentration of interleukin-6 could be an indicator of progression to encephalopathy, thus the direct viral invasion might not be responsible for all of the symptoms. 25,26 The study of Kamimura et al reported that in a studied group most fatal cases of influenza-associated acute encephalopathy/encephalitis occurred in the first influenza infection, and that these patients had not been immunized.…”

“…Influenza‐related acute encephalopathy/encephalitis is rarely seen except in cases of Reye syndrome, and epidemics have rarely been reported in other countries 12−21 . Some studies in Japan have provided direct evidence of the influenza virus genome in cerebrospinal fluid 22−24 . However, recent studies indicate that several cytokines might mediate the disease and a high plasma concentration of interleukin‐6 could be an indicator of progression to encephalopathy, thus the direct viral invasion might not be responsible for all of the symptoms 25,26 .…”

Encephalitis Associated with Influenza B Virus Infection in 2 Children and a Review of the Literature

“…In the English-language literature, 21 cases of IBAE have been reported [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Eight cases were excluded from this analysis: 4 were reported in articles that contained insufficient information for analysis [15][16][17][18], 3 were reported in studies that failed to provide adequate serologic or cell culture-based evidence of influenza B virus infection [6,19], and one case may have been Reye syndrome [20].…”