Genetic relatedness of infecting and reinfecting respiratory syncytial virus strains identified in a birth cohort from rural Kenya

Abstract

Background: Respiratory syncytial virus (RSV) reinfects individuals repeatedly. The extent to which this is a consequence of RSV antigenic diversity is unclear.

Methods: Six-hundred thirty-five children from rural Kenya were closely monitored for RSV infection from birth through 3 consecutive RSV epidemics. RSV infections were identified by immunofluorescence testing of nasal washing samples collected during acute respiratory illnesses, typed into group A and B, and sequenced in the attachment (G) protein. A positive sample separated from a previous positive by ≥14 days was defined as a reinfection a priori.

Results: Phylogenetic analysis was undertaken for 325 (80%) of 409 identified infections, including 53 (64%) of 83 reinfections. Heterologous group reinfections were observed in 28 episodes, and homologous group reinfections were observed in 25 episodes; 10 involved homologous genotypes, 5 showed no amino acid changes, and 3 were separated by 21-24 days and were potentially persistent infections. The temporal distribution of genotypes among reinfections did not differ from that of single infections.

Conclusions: The vast majority of infection and reinfection pairs differed by group, genotype, or G amino acid sequence (ie, comprised distinct viruses). The extent to which this is a consequence of immune memory of infection history or prevalent diversity remains unclear.

Figure 1.

The time course of 53 RSV infections in the 52 children who had repeat infection. The different subplots represent the group reinfection patterns observed. In the subplots, the dotted portions of the black horizontal straight lines represent the time from birth to the first positive sample of a reinfected participant. Each symbol between the continuous portions of the horizontal line represents a positive sample for which genotyping was completed: empty red circle, GA2; a red x symbol, GA5; empty blue triangle, SAB1 and filled blue square, BA. The continuous red curve and the dotted blue curve represent the monthly trends in the number of RSV A and RSV B cases detected, respectively, in the whole cohort, shown by the secondary y-axis.

Figure 2.

Maximum likelihood phylogenetic tree based on the sequences from the 12 subjects who experienced homologous group A reinfections. Reference sequences for genotypes GA1-7 and SAA1-3 were included to assign the strains G genotypes. The GenBank accession numbers of the reference sequences are Aus/A2/1961, M11486; CH57,AF065258 ; NZA_91_05, DQ171722; CH9, AF065254; CH17, AF065255; NZA_89_04, DQ171761, NZA_90_02, DQ171755; and NZA_98_01, DQ171792. The empty triangles represent first infections, and the dark, filled triangles represent the repeat infections.

Figure 3.

A maximum likelihood tree showing the evolutionary relationship of strains from subjects who experienced homologous group B reinfections. The tree is based on sequences from 11 subjects and reference sequences representing genotypes GB1-4, SAB1-3 and the BA. Their GenBank accession numbers are CH10b, AF065250; CH93-9B,AF065251; CH93-53B, AF065253; BE/400/91, AY751275; BE/12252/96, AY751241; BE/1054/98,DQ985156; Uru/41605; AF251557; and Arg//3997/1999, DQ227366. The empty triangles represent first infections, and the dark, filled triangles represent the second infections.