Abstract
Human respiratory syncytial virus (HRSV) has three surface glycoproteins: small hydrophobic (SH), attachment (G) and fusion (F), encoded by three consecutive genes (SH-G-F). A 270-nt fragment of the G gene is used to genotype HRSV isolates. This study genotyped and investigated the variability of the gene and amino acid sequences of the three surface proteins of HRSV strains collected from 1987 to 2005 from one center. Sixty original clinical isolates and 5 prototype strains were analyzed. Sequences containing SH, F and G genes were generated, and multiple alignments and phylogenetic trees were analyzed. Genetic variability by protein domains comparing virus genotypes was assessed. Complete sequences of the SH-G-F genes were obtained for all 65 samples: HRSV-A = 35; HRSV-B = 30. In group A strains, genotypes GA5 and GA2 were predominant. For HRSV-B strains, the genotype GB4 was predominant from 1992 to 1994 and only genotype BA viruses were detected in 2004–2005. Different genetic variability at nucleotide level was detected between the genes, with G gene being the most variable and the highest variability detected in the 270-nt G fragment that is frequently used to genotype the virus. High variability (>10%) was also detected in the signal peptide and transmembrane domains of the F gene of HRSV A strains. Variability among the HRSV strains resulting in non-synonymous changes was detected in hypervariable domains of G protein, the signal peptide of the F protein, a not previously defined domain in the F protein, and the antigenic site Ø in the pre-fusion F. Divergent trends were observed between HRSV -A and -B groups for some functional domains. A diverse population of HRSV -A and -B genotypes circulated in Houston during an 18 year period. We hypothesize that diverse sequence variation of the surface protein genes provide HRSV strains a survival advantage in a partially immune-protected community.
Highlights
Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory disease among infants [1,2], a frequent pathogen in elderly and immunosuppressed patients [3] and a major public health concern worldwide [4]
The analyzed genes (SH-G-F) from HRSV-A samples corresponded to nucleotides 4,171 to 7,630 in the reference strain A2 from Genbank
The molecular epidemiology of HRSV is based on the phylogeny of the second hypervariable region of G gene [10]
Summary
Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory disease among infants [1,2], a frequent pathogen in elderly and immunosuppressed patients [3] and a major public health concern worldwide [4]. The analysis of the nucleotide sequence on the second hypervariable region of the G gene has led to classification of HRSV genotypes within HRSV -A and -B groups [10] and revealed that multiple genotypes can cocirculate during the same epidemic season [10,11]. Similar to the ON1 genotype, a 60 nt-duplication in the G gene of HRSV-B was identified in 1998 in Buenos Aires. This novel HRSV-B subgroup was named BA genotype [24], and spread worldwide within a 7 years period, replacing the other prevailing HRSV-B genotypes by 2005. No consistent association has been established between severity of disease and HRSV genotype
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