Abstract
Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a “flip-flop” phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.
Highlights
Human respiratory syncytial virus (HRSV) is a leading cause of severe acute respiratory infection in childhood worldwide [1] and an important agent of acute respiratory infection in the elderly and immunocompromised [2,3]
The genotypes of HRSVA and B show complex fluctuating dynamics, since they may co-circulate during a given season, with one or two dominant genotypes that are replaced in consecutive years [6,7,8,9,10,11]
HRSV sequencing and genotyping We obtained nucleotide sequences of the second region (G2) of the HRSV G protein gene from (i) 432 random samples collected over 11 seasons from the city of Sao Paulo, Brazil and (ii) 136 sequences from samples collected by Viral Genetic Diversity Network (VGDN) program from 2004 to 2005 from metropolitan area of the city of Sao Paulo and from the city of Ribeirao Preto, in Sao Paulo state
Summary
Human respiratory syncytial virus (HRSV) is a leading cause of severe acute respiratory infection in childhood worldwide [1] and an important agent of acute respiratory infection in the elderly and immunocompromised [2,3]. Initial studies with monoclonal antibodies to the HRSV F and G proteins divided the virus into two major groups (A and B) [4,5]. The deduced amino acid sequences of the G protein are highly divergent, with a sequence identity of approximately 53% between HRSVA and B, and 20% divergence within the same antigenic group [14,19]. Despite this diversity, the nature of the selection pressures acting on the G protein have not Author Summary
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