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. 2020 Jul;14(4):403-411.
doi: 10.1111/irv.12727. Epub 2020 Mar 3.

Characterization of human respiratory syncytial virus (RSV) isolated from HIV-exposed-uninfected and HIV-unexposed infants in South Africa during 2015-2017

Hui Liu  1 , Bin Lu  1 , David E Tabor  1 , Andrey Tovchigrechko  2 , Deidre Wilkins  2 , Hong Jin  1 , Shabir A Madhi  3   4 , Nasiha Soofie  3   4 , Mark T Esser  2 , Marta C Nunes  3   4
Affiliations

Characterization of human respiratory syncytial virus (RSV) isolated from HIV-exposed-uninfected and HIV-unexposed infants in South Africa during 2015-2017

Hui Liu et al. Influenza Other Respir Viruses. 2020 Jul.

Abstract

Background: RSV is a leading cause of lower respiratory tract infection in infants. Monitoring RSV glycoprotein sequences is critical for understanding RSV epidemiology and viral antigenicity in the effort to develop anti-RSV prophylactics and therapeutics.

Objectives: The objective is to characterize the circulating RSV strains collected from infants in South Africa during 2015-2017.

Methods: A subset of 150 RSV-positive samples obtained in South Africa from HIV-unexposed and HIV-exposed-uninfected infants from 2015 to 2017, were selected for high-throughput next-generation sequencing of the RSV F and G glycoprotein genes. The RSV G and F sequences were analyzed by a bioinformatic pipeline and compared to the USA samples from the same three-year period.

Results: Both RSV A and RSV B co-circulated in South Africa during 2015-2017, with a shift from RSV A (58%-61% in 2015-2016) to RSV B (69%) in 2017. RSV A ON1 and RSV B BA9 genotypes emerged as the most prevalent genotypes in 2017. Variations at the F protein antigenic sites were observed for both RSV A and B strains, with dominant changes (L172Q/S173L) at antigenic site V observed in RSV B strains. RSV A and B F protein sequences from South Africa were very similar to the USA isolates except for a higher rate of RSV A NA1 and RSV B BA10 genotypes in South Africa.

Conclusion: RSV G and F genes continue to evolve and exhibit both local and global circulation patterns in South Africa, supporting the need for continued national surveillance.

Keywords: G and F proteins; RSV; antigenic sites; monoclonal antibodies.

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Conflict of interest statement

HL, BL, DET, AT, DW, HJ, and MTE are employees and shareholders of AstraZeneca when the study was conducted; SAM, NS and MCN had no competing interests.

Figures

Figure 1
Figure 1
RSV‐positive sample consort diagram and distribution of RSV subtypes and genotypes by sample collection month over 2015 to 2017. A. Representative RSV‐positive (n = 150) samples from HIV‐unexposed (HU) (n = 544) and HIV‐exposed‐uninfected (HEU) infants (n = 198) from the 2015‐2017 RSV seasons in South Africa were selected for sequencing. The sample collection year, HIV exposure status, and RSV A or B subtype are shown. B. The subtypes and genotypes were determined from the 147 sequenced samples collected from January 2015 to December 2017
Figure 2
Figure 2
Phylogenetic trees based on the second hypervariable region of the G protein. The reference sequences KX858754 and KX858755 were used to root RSV A G and B G trees, respectively. The evolutionary history was inferred by using the maximum likelihood method based on the JTT matrix‐based model in mega7. Phylogenetic trees were visualized and annotated using ITOL v3. Genotypes are indicated by leaf color (RSVA: NA1 orange, ON1 green, RSV B: BA9 blue, BA10 yellow). Year of sample collection and the HIV exposure status (HEU red, HU black) are indicated by the presence of a filled bar in the respective year column. RSV B: sample names in purple indicate G protein extension, brown indicates truncation
Figure 3
Figure 3
Polymorphisms in the RSV A and B Fusion proteins. A, Plots of amino acid variation frequency by position of F protein open reading frame (1‐574) compared to the KX858757 (RSV A F) and KX858756 (RSV B F) reference sequences based on year. SP, signal peptide; P27, cleaved peptide of 27 AA residues, TM, transmembrane domain, CT, cytoplasmic tail. Red, RSV A; Blue, RSV B. Variations at a frequency >10% (dashed lines) in each season relative to the references are labeled. B, Polymorphisms observed in the antigenic sites of RSV F protein. RSV F protein pre‐fusion and post‐fusion conformations were based on the Protein Data Bank files of 5UDE and 3RRR, respectively. Antigenic sites (Ø, I, II, III, IV, and V) are colored. Red: site Ø, blue: I, yellow: II, green: III, purple: IV, orange: V. Amino acid variations in these antigenic sites and their frequency for each season are listed in the tables on the right. AIndicates variation only showed in RSV A. A/BIndicates residues that showed variations in both RSV A and RSV B. Other numbers indicate variations in RSV B only
Figure 4
Figure 4
Phylogenetic analysis of RSV A and B Fusion proteins from South Africa and USA (2015‐17). Phylogenetic trees were generated by using the maximum likelihood method based on the JTT matrix‐based model in mega7. Trees were visualized and annotated using ITOL v3. Genotypes are indicated by color ring
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