Asian Zika virus can acquire generic African-lineage mutations during in utero infection
The Zika virus 2015 epidemic showed an unusual phenotype for human flaviviruses, specifically fetal infection. We previously showed that in utero inoculation with the Asian Zika virus isolated from the human sample causes persistent infection in porcine fetuses. Here, we characterized the evolution...
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Taylor & Francis Group
2023-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2263592 |
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| author | Ahmad Jawad Sabir Prince Pal Singh Ivan Trus Nguyen Phuong Khanh Le Uladzimir Karniychuk |
| author_facet | Ahmad Jawad Sabir Prince Pal Singh Ivan Trus Nguyen Phuong Khanh Le Uladzimir Karniychuk |
| author_sort | Ahmad Jawad Sabir |
| collection | DOAJ |
| description | The Zika virus 2015 epidemic showed an unusual phenotype for human flaviviruses, specifically fetal infection. We previously showed that in utero inoculation with the Asian Zika virus isolated from the human sample causes persistent infection in porcine fetuses. Here, we characterized the evolution of the Asian Zika virus in the fetal brain and placenta. Interestingly, the Asian Zika virus acquired generic African lineage K101R (A408G) and R1609 K (G4932A) mutations during in utero infection. Both African mutations were nonsynonymous and had a high frequency of nearly 100% in the fetal brain. Then, we synthetically generated the wild-type Asian variant and fetal brain-specific variant with generic African-lineage K101R and R1609 K mutations. In mosquito C6/36 cells, but not in human and pig cells, the fetal brain-specific variant showed higher virus loads compared to the Asian wild-type prototype. While in utero infection with both variants caused comparable virus loads in the placenta and amniotic fluids, fetuses injected with the fetal brain-specific variant had the trend to higher virus loads in lymph nodes. Also, introduced K101R and R1609 K mutations were stable and had high nearly 100% frequency at 28 days after in utero inoculation in both directly injected and trans-infected fetuses. These findings evoke concerns because Zika persists in pig herds and mosquitoes on farms in Mexico. It will be essential to identify how persistent in utero infection affects virus evolution and whether in utero-emerged Zika variants have the potential for shedding into the environment, more efficient transmission, and more aggressive infection phenotypes. |
| format | Article |
| id | doaj-art-da1698fa6c1941da87cef6cd1e7d58e3 |
| institution | DOAJ |
| issn | 2222-1751 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-da1698fa6c1941da87cef6cd1e7d58e32025-08-20T03:14:59ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2263592Asian Zika virus can acquire generic African-lineage mutations during in utero infectionAhmad Jawad Sabir0Prince Pal Singh1Ivan Trus2Nguyen Phuong Khanh Le3Uladzimir Karniychuk4Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, CanadaSchool of Public Health, University of Saskatchewan, Saskatoon, CanadaDioscuri Centre for RNA-Protein Interactions in Human Health and Disease, International Institute of Molecular and Cell Biology, Warsaw, PolandDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USASchool of Public Health, University of Saskatchewan, Saskatoon, CanadaThe Zika virus 2015 epidemic showed an unusual phenotype for human flaviviruses, specifically fetal infection. We previously showed that in utero inoculation with the Asian Zika virus isolated from the human sample causes persistent infection in porcine fetuses. Here, we characterized the evolution of the Asian Zika virus in the fetal brain and placenta. Interestingly, the Asian Zika virus acquired generic African lineage K101R (A408G) and R1609 K (G4932A) mutations during in utero infection. Both African mutations were nonsynonymous and had a high frequency of nearly 100% in the fetal brain. Then, we synthetically generated the wild-type Asian variant and fetal brain-specific variant with generic African-lineage K101R and R1609 K mutations. In mosquito C6/36 cells, but not in human and pig cells, the fetal brain-specific variant showed higher virus loads compared to the Asian wild-type prototype. While in utero infection with both variants caused comparable virus loads in the placenta and amniotic fluids, fetuses injected with the fetal brain-specific variant had the trend to higher virus loads in lymph nodes. Also, introduced K101R and R1609 K mutations were stable and had high nearly 100% frequency at 28 days after in utero inoculation in both directly injected and trans-infected fetuses. These findings evoke concerns because Zika persists in pig herds and mosquitoes on farms in Mexico. It will be essential to identify how persistent in utero infection affects virus evolution and whether in utero-emerged Zika variants have the potential for shedding into the environment, more efficient transmission, and more aggressive infection phenotypes.https://www.tandfonline.com/doi/10.1080/22221751.2023.2263592Zika virusflavivirusevolutionmutationfetuspersistence |
| spellingShingle | Ahmad Jawad Sabir Prince Pal Singh Ivan Trus Nguyen Phuong Khanh Le Uladzimir Karniychuk Asian Zika virus can acquire generic African-lineage mutations during in utero infection Emerging Microbes and Infections Zika virus flavivirus evolution mutation fetus persistence |
| title | Asian Zika virus can acquire generic African-lineage mutations during in utero infection |
| title_full | Asian Zika virus can acquire generic African-lineage mutations during in utero infection |
| title_fullStr | Asian Zika virus can acquire generic African-lineage mutations during in utero infection |
| title_full_unstemmed | Asian Zika virus can acquire generic African-lineage mutations during in utero infection |
| title_short | Asian Zika virus can acquire generic African-lineage mutations during in utero infection |
| title_sort | asian zika virus can acquire generic african lineage mutations during in utero infection |
| topic | Zika virus flavivirus evolution mutation fetus persistence |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2263592 |
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