Genomic Surveillance of enteric viruses

Professor

Senior Research Fellow

Project Background

Rotaviruses are segmented, double-stranded RNA viruses. Their genetic diversity is mainly driven by genetic drift due to the error-prone RNA-dependent RNA polymerase, genetic shift due to gene segment reassortment of genes. Rotavirus vaccines have been shown to be highly effective at preventing moderate to severe diarrhoeal disease in children, especially in high-income countries compared to low-income settings where the highest rotavirus disease burden occurs. Rotavirus vaccination prevents disease, but does not result in sterilizing immunity and thus subsequent re-infection is possible. Rotavirus vaccines, therefore, create an immune environment that exerts novel selective pressures on the circulating wildtype virus population. It is crucial to understand the consequences of vaccination on the circulating wildtype rotavirus population and the mechanisms underlying vaccine escape. Understanding the pattern of virus emergence will inform vaccine design and assist in maintaining an effective and successful global rotavirus vaccine program.

Objectives/Research Areas

Employing the power of next generation sequencing (NGS), the primary research objectives include the following:

To completely characterize whole genomes of historical and contemporary rotaviruses in Ghana.
To investigate the evolutionary dynamics of prevalent human rotaviruses pre- and post-vaccine introduction in selected African countries, and the impact of emerging and/or re-emerging strains on rotavirus epidemiology.
To determine the impact of rotavirus vaccine introduction on the evolution of circulating rotavirus strains at genome level in selected African countries.
To identify genomic regions, if any, that may be under selection pressure resulting from vaccine introduction.

Key Findings

Accumulation of point mutations over time in rotavirus genes is a major driver of the observed rotavirus genetic diversity in Ghana.

- Evidence of multiple, independent interspecies transmission and reassortment events between co-circulating rotavirus strains as a contributor to the extensive genetic diversity observed in Ghanaian rotaviruses.

Detection of the first G6P[14] human-artiodactyl reassortant rotavirus strain in a Ghanaian child

Identification of novel G8P[6] human-bovine reassortant rotavirus strains in Ghanaian children

Detection of G4P[6] porcine-human reassortant, and G4P[6] porcine rotaviruses in Ghanaian children

G3P[6] rotaviruses with an artiodactyl-like NSP2 gene observed in the post-vaccine introduction era

The emergence and re-emergence of some strains and/or lineages is cyclical. However, some strains/lineages are almost always present.
Emerging, unusual G1P[8], G3P[8] and G8P[8] and G9P[4] reassortant strains share lineage constellations with contemporary G2P[4] strains, lending strong support to the hypothesis that such unusual genotype 2 strains originated primarily from reassortment events in the recent past involving contemporary G2P[4] strains and ordinary genotype 1, genotype 2 or animal RVA strains as another

Ongoing Activities

African Enteric Viruses Genome Initiative: Impact of RotarixTM vaccine introduction on genome evolution of human rotaviruses in Ghana (2018-2022)

Molecular epidemiology of viral agents of gastroenteritis in Ghanaian children less than 5 years old (2015 – to date)

Full genome‐based classification of Group A rotaviruses isolated from Ghanaian children (2010 – 2018)

Key Publications

Mwangi PN, Page NA, Seheri ML, Mphahlele MJ, Nadan, S, Esona MD, Kumwenda B, Kamng’ona AW, Donato CM, Steele DA, Ndze VN, Dennis FE, Jere KC, and Nyaga MM (2022). Evolutionary changes between pre- and post- vaccine South African group A G2P[4] rotavirus strains, 2003–2017. Microbial Genomes, 8(4).
doi: 10.1099/mgen.0.000809

Mwangi PN, Mogotsi MT, Seheri ML, Mphahlele MJ, Peenze I, Esona MD, Kumwenda B, Steele AD, Kirkwood CD, Ndze VN, Dennis FE, Jere KC, Nyaga MM (2020). Whole Genome In-Silico Analysis of South African G1P[8] Rotavirus Strains Before and After Vaccine Introduction Over A Period of 14 Years. Vaccines. 8(4):E609.
doi: 10.3390/vaccines8040609

Mwangi PN, Mogotsi MT, Rasebotsa SP, Seheri ML, Mphahlele MJ, Ndze VN, Dennis FE, Jere KC, Nyaga MM (2020). Uncovering the First Atypical DS-1-like G1P[8] Rotavirus Strains That Circulated during Pre-Rotavirus Vaccine Introduction Era in South Africa. Pathogens. 9(5):391.
doi: 10.3390/pathogens9050391

Nyaga MM, Sabiu S, Ndze VN, Dennis FE, Jere KC (2020). Report of the 1st African Enteric Viruses Genome Initiative (AEVGI) Data and Bioinformatics Workshop on whole-genome analysis of some African rotavirus strains held in Bloemfontein, South Africa. Vaccine. 38(34):5402-5407.
doi: 10.1016/j.vaccine.2020.06.010

Damanka SA, Dennis FE, Lartey BL, Nyarko KM, Agbemabiese CA, Armah GE (2020). Next-generation sequencing of a human-animal reassortant G6P[14] rotavirus A strain from a child hospitalized with diarrhoea. Arch Virol. 165(4):1003-1005.
doi: 10.1007/s00705-020-04543-4

Damanka SA, Kwofie S, Dennis FE, Lartey BL, Agbemabiese CA, Doan YH, Adiku TK, Katayama K, Enweronu-Laryea CC, Armah GE (2019). Whole genome characterization and evolutionary analysis of OP354-like P[8] Rotavirus A strains isolated from Ghanaian children with diarrhoea. PLoS One. 14(6):e0218348.
doi: 10.1371/journal.pone.0218348

Agbemabiese CA, Nakagomi T, Damanka SA, Dennis FE, Lartey BL, Armah GE, Nakagomi O (2019). Sub-genotype phylogeny of the non-G, non-P genes of genotype 2 Rotavirus A strains. PLoS One.14(5):e0217422.
doi: 10.1371/journal.pone.0217422

Agbemabiese CA, Nakagomi T, Doan YH, Do LP, Damanka S, Armah GE, Nakagomi O (2016). Genomic constellation and evolution of Ghanaian G2P[4] rotavirus strains from a global perspective. Infect Genet Evol. 45:122-131.
doi: 10.1016/j.meegid.2016.08.024

Agbemabiese CA, Nakagomi T, Suzuki Y, Armah G, Nakagomi O (2015). Evolution of a G6P[6] rotavirus strain isolated from a child with acute gastroenteritis in Ghana, 2012. J Gen Virol. 96(8):2219-31.
doi:10.1099/vir.0.000174

Dennis FE, Fujii Y, Haga K, Damanka S, Lartey B, Agbemabiese CA, Ohta N, Armah GE, Katayama K (2014). Identification of Novel Ghanaian G8P[6] Human-Bovine Reassortant Rotavirus Strain by Next Generation Sequencing. PLoS ONE. 9(6): e100699.
doi: 10.1371/journal.pone.0100699

Komoto S, Pongsuwanna Y, Ide T, Wakuda M, Guntapong R, Dennis FE, Haga K, Fujii Y, Katayama K, Taniguchi K (2014). Whole genomic analysis of porcine G10P[5] rotavirus strain P343 provides evidence for bovine-to-porcine interspecies transmission. Veterinary Microbiology. 174(3-4): 577-583.
doi: 10.1016/j.vetmic.2014.09.033

Team