Showing papers by "Stephen Lindstrom published in 2001"

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. J. Med. Virol. 65:590–597, 2001. © 2001 Wiley-Liss, Inc.

Analyses of evolutionary and virulence divergency of Hong Kong H5N1 influenza A viruses isolated from humans

Abstract: Nucleotide and amino acid sequence homologies of the entire RNA segments of six H5N1 human influenza viruses were divided into two or three variant groups. This result was compatible with that of phylogenetic analysis, which showed that trees of the eight genes were composed of two or three minor branch clusters. The PB2, PA, NP and M proteins of human H5N1 viruses were further characterized by the presence of previously reported amino acid sequences peculiar to those of human strains. The virulence of A/Hong Kong/483/97 (HK483) in mice exhibited a sharp contrast to that of A/Hong Kong/156/97 (HK156). Virulence of the former even remained after constant repeated passage in eggs, while the latter rapidly decreased in virulence for mice after only a few passages in eggs. It became apparent that Madin–Darby canine kidney (MDCK) cell-grown virus (HK156-CK) and its clones derived from mouse brain produced a fatal infection in mice through intranasal (i.n.) or intracerebral (i.c.) routes. Conversely, the pathogenicity shown by the egg-derived parental virus (HK156-E3) and its clones were considerably lower in mice after i.n. or i.c. infection. A series of experimental infections revealed that the marked differences in neurovirulence among viruses could be attributed to whether or not viruses were transmitted from the lung to the brain. In amino acid sequence comparison of the entire proteins, it was suggested that a total of six amino acid differences in the PB1(residues 456 and 712), PA (residue 631), HA (residue 211), NP (residue 127) and NS1 (residue101) proteins related closely to changes in pathogenicity or neurovirulence of the HK156 virus in mice. As a result, it was evident that less pathogenic and neurovirulent strains appeared through adaptation and selection of variants during passage in eggs.