Respiratory syncytial virus genetic and antigenic diversity

Abstract

Respiratory syncytial virus (RSV) is a major cause of viral lower respiratory tract infections among infants and young children in both developing and developed countries. There are two major antigenic groups of RSV, A and B, and additional antigenic variability occurs within the groups. The most extensive antigenic and genetic diversity is found in the attachment glycoprotein, G. During individual epidemic periods, viruses of both antigenic groups may cocirculate or viruses of one group may predominate. When there are consecutive annual epidemics in which the same group predominates, the dominant viruses are genetically different from year to year. The antigenic differences that occur among these viruses may contribute to the ability of RSV to establish reinfections throughout life. The differences between the two groups have led to vaccine development strategies that should provide protection against both antigenic groups. The ability to discern intergroup and intragroup differences has increased the power of epidemiologic investigations of RSV. Future studies should expand our understanding of the molecular evolution of RSV and continue to contribute to the process of vaccine development.

FIG. 1

Variable and conserved domains of the G protein. (A) The primary amino acid structure of the G protein of the A2 isolate of RSV is shown. The cytoplasmic tail (cyto), transmembrane domain (tm, solid), and ectodomain are marked. Amino acid numbers are shown below the linear figure. The location of the four conserved cysteine residues in the ectodomain is shown (cccc). (B) The 13-amino-acid region that is strictly conserved among all naturally occurring human RSV G proteins is indicated (amino acids 164 to 176). (C) The linear regions of the G protein that are relatively conserved or variable within and between the antigenic groups are shown.

FIG. 2

Group A (A) and B (B) RSV G-protein phylogenetic relationships. Partial G-protein sequences from RSV strains isolated in the Children's Hospital of Alabama were compared to published G-protein sequences available through GenBank (25). Viruses are identified by the geographic location (from the United States, al, Alabama; wv, West Virginia [114]; dc, District of Columbia [67]; ma, Massachusetts [114]; md, Maryland [67]; nm, New Mexico [114]; from the United Kingdom, uk [15]; from Spain, mad, Madrid; from Uruguay, mon, Montevideo [46]; from Sweden, swed [112]; and from Australia, aus [134]), year of isolation (or number and year for isolates from Montevideo and Madrid), and, for isolates from the United States and the United Kingdom, a number designation. Nucleotide sequence alignments of either group A or group B sequences were used to create the neighbor-joining trees in the figure. The scales represent either 0.02 (group A) or 0.01 (group B) substitutions per base per indicated horizontal distance. The numbers present at some of the internal nodes of the trees represent the number of bootstrap replicates of a total of 1,000 that display the indicated sequence groupings. Only significant bootstrap replicate numbers with values greater than 800 are shown. Tentative assignments to the genotypes described by Peret et al. (94) are indicated by the brackets and the designations GA1, GA2, GA3, GA5, GB1, GB3, and GB4.

FIG. 2

Group A (A) and B (B) RSV G-protein phylogenetic relationships. Partial G-protein sequences from RSV strains isolated in the Children's Hospital of Alabama were compared to published G-protein sequences available through GenBank (25). Viruses are identified by the geographic location (from the United States, al, Alabama; wv, West Virginia [114]; dc, District of Columbia [67]; ma, Massachusetts [114]; md, Maryland [67]; nm, New Mexico [114]; from the United Kingdom, uk [15]; from Spain, mad, Madrid; from Uruguay, mon, Montevideo [46]; from Sweden, swed [112]; and from Australia, aus [134]), year of isolation (or number and year for isolates from Montevideo and Madrid), and, for isolates from the United States and the United Kingdom, a number designation. Nucleotide sequence alignments of either group A or group B sequences were used to create the neighbor-joining trees in the figure. The scales represent either 0.02 (group A) or 0.01 (group B) substitutions per base per indicated horizontal distance. The numbers present at some of the internal nodes of the trees represent the number of bootstrap replicates of a total of 1,000 that display the indicated sequence groupings. Only significant bootstrap replicate numbers with values greater than 800 are shown. Tentative assignments to the genotypes described by Peret et al. (94) are indicated by the brackets and the designations GA1, GA2, GA3, GA5, GB1, GB3, and GB4.