Emergence of human G2P[4] rotaviruses containing animal derived gene segments in the post-vaccine era

Zeller, Mark; Nuyts, Valerie; Heylen, Elisabeth; Coster, Sarah De; Conceição-Neto, Nádia; Ranst, Marc Van; Matthijnssens, Jelle

doi:10.1038/srep36841

Cited by 13 publications

(13 citation statements)

References 33 publications

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“…There is evidence for frequent inter-host-species reassortment of segment 10, which encodes the enterotoxin, NSP4, in nature [ 15 , 100 ], so reassortment of segment 10 may be more dependent on the sequence conservation of terminal +ssRNA between segments 10 and 11, than on protein interactions. In addition to NSP5, segment 11 also encodes a second out of frame protein, NSP6, via leaky scanning.…”

Section: Discussionmentioning

confidence: 99%

Rotavirus A Genome Segments Show Distinct Segregation and Codon Usage Patterns

Dennehy

2021

Viruses

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Reassortment of the Rotavirus A (RVA) 11-segment dsRNA genome may generate new genome constellations that allow RVA to expand its host range or evade immune responses. Reassortment may also produce phylogenetic incongruities and weakly linked evolutionary histories across the 11 segments, obscuring reassortment-specific epistasis and changes in substitution rates. To determine the co-segregation patterns of RVA segments, we generated time-scaled phylogenetic trees for each of the 11 segments of 789 complete RVA genomes isolated from mammalian hosts and compared the segments’ geodesic distances. We found that segments 4 (VP4) and 9 (VP7) occupied significantly different tree spaces from each other and from the rest of the genome. By contrast, segments 10 and 11 (NSP4 and NSP5/6) occupied nearly indistinguishable tree spaces, suggesting strong co-segregation. Host-species barriers appeared to vary by segment, with segment 9 (VP7) presenting the weakest association with host species. Bayesian Skyride plots were generated for each segment to compare relative genetic diversity among segments over time. All segments showed a dramatic decrease in diversity around 2007 coinciding with the introduction of RVA vaccines. To assess selection pressures, codon adaptation indices and relative codon deoptimization indices were calculated with respect to different host genomes. Codon usage varied by segment with segment 11 (NSP5) exhibiting significantly higher adaptation to host genomes. Furthermore, RVA codon usage patterns appeared optimized for expression in humans and birds relative to the other hosts examined, suggesting that translational efficiency is not a barrier in RVA zoonosis.

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Section: Discussionmentioning

confidence: 99%

Rotavirus A Genome Segments Show Distinct Segregation and Codon Usage Patterns

Dennehy

2021

Viruses

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“…An alternative explanation is that continuous natural variation of cocirculating rotavirus genotypes, along with other poorly understood factors, contributes significantly to fluctuations in global and regional genotype landscapes. The effects of vaccines on rotavirus populations also may be more complex than simple serotype selection, as suggested by increased detection of G2P [4] reassortants containing animal-derived segments and of G1P [8] rotaviruses containing segments genetically distinct from those of RV1 in postvaccine versus prevaccine years in Belgium (83,84). Additional surveillance and directed studies will help to clarify the specific roles of RV1 and RV5 in rotavirus selection and evolution.…”

Section: Discussionmentioning

confidence: 99%

Multiple Introductions and Antigenic Mismatch with Vaccines May Contribute to Increased Predominance of G12P[8] Rotaviruses in the United States

Ogden

Tan

Akopov

et al. 2019

J Virol

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Rotavirus is the leading global cause of diarrheal mortality for unvaccinated children under 5 years of age. The outer capsid of rotavirus virions consists of VP7 and VP4 proteins, which determine viral G and P types, respectively, and are primary targets of neutralizing antibodies. Successful vaccination depends upon generating broadly protective immune responses following exposure to rotaviruses presenting a limited number of G- and P-type antigens. Vaccine introduction resulted in decreased rotavirus disease burden but also coincided with the emergence of uncommon G and P genotypes, including G12. To gain insight into the recent predominance of G12P[8] rotaviruses in the United States, we evaluated 142 complete rotavirus genome sequences and metadata from 151 clinical specimens collected in Nashville, TN, from 2011 to 2013 through the New Vaccine Surveillance Network. Circulating G12P[8] strains were found to share many segments with other locally circulating strains but to have distinct constellations. Phylogenetic analyses of G12 sequences and their geographic sources provided evidence for multiple separate introductions of G12 segments into Nashville, TN. Antigenic epitopes of VP7 proteins of G12P[8] strains circulating in Nashville, TN, differ markedly from those of vaccine strains. Fully vaccinated children were found to be infected with G12P[8] strains more frequently than with other rotavirus genotypes. Multiple introductions and significant antigenic mismatch may in part explain the recent predominance of G12P[8] strains in the United States and emphasize the need for continued monitoring of rotavirus vaccine efficacy against emerging rotavirus genotypes. IMPORTANCE Rotavirus is an important cause of childhood diarrheal disease worldwide. Two immunodominant proteins of rotavirus, VP7 and VP4, determine G and P genotypes, respectively. Recently, G12P[8] rotaviruses have become increasingly predominant. By analyzing rotavirus genome sequences from stool specimens obtained in Nashville, TN, from 2011 to 2013 and globally circulating rotaviruses, we found evidence of multiple introductions of G12 genes into the area. Based on sequence polymorphisms, VP7 proteins of these viruses are predicted to present themselves to the immune system very differently than those of vaccine strains. Many of the sick children with G12P[8] rotavirus in their diarrheal stools also were fully vaccinated. Our findings emphasize the need for continued monitoring of circulating rotaviruses and the effectiveness of the vaccines against strains with emerging G and P genotypes.

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“…In contrast, the current study clearly indicates the emergence of G2P[4] strains, representing more than 35.9% of rotavirus infections in Seoul from March 2013 to August 2015. G2P[4] genotype was predominant in many other countries, including Belgium, Austria, Brazil, and Australia, where the Rotarix vaccine was introduced 11 – 15 , 30 , 31 . However, the samples in this study were collected from Seoul, where vaccination in children is optional (by parental choice) and administered according to opportunity and availability, with RotaTeq being more popular than Rotarix 32 .…”

Section: Discussionmentioning

confidence: 99%

Emergence of Human G2P[4] Rotaviruses in the Post-vaccination Era in South Korea: Footprints of Multiple Interspecies Re-assortment Events

Thanh

Tran

Lim

et al. 2018

Sci Rep

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After the introduction of two global rotavirus vaccines, RotaTeq in 2007 and Rotarix in 2008 in South Korea, G1[P8] rotavirus was the major rotavirus genotype in the country until 2012. However, in this study, an emergence of G2P[4] as the dominant genotype during the 2013 to 2015 season has been reported. Genetic analysis revealed that these viruses had typical DS-1-like genotype constellation and showed evidence of re-assortment in one or more genome segments, including the incorporation of NSP4 genes from strains B-47/2008 from a cow and R4/Haryana/2007 from a buffalo in India, and the VP1 and VP3 genes from strain GO34/1999 from a goat in Bangladesh. Compared to the G2 RotaTeq vaccine strain, 17–24 amino acid changes, specifically A87T, D96N, S213D, and S242N substitutions in G2 epitopes, were observed. These results suggest that multiple interspecies re-assortment events might have contributed to the emergence of G2P[4] rotaviruses in the post-vaccination era in South Korea.

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Emergence of human G2P[4] rotaviruses containing animal derived gene segments in the post-vaccine era

Cited by 13 publications

References 33 publications

Rotavirus A Genome Segments Show Distinct Segregation and Codon Usage Patterns

Rotavirus A Genome Segments Show Distinct Segregation and Codon Usage Patterns

Multiple Introductions and Antigenic Mismatch with Vaccines May Contribute to Increased Predominance of G12P[8] Rotaviruses in the United States

Emergence of Human G2P[4] Rotaviruses in the Post-vaccination Era in South Korea: Footprints of Multiple Interspecies Re-assortment Events

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