Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation
Abstract Zika virus (ZIKV) is a potential threat to male reproductive health but the mechanisms underlying its influence on testes during ZIKV infection remain obscure. To address this question, we perform single-cell RNA sequencing using testes from ZIKV-infected mice. The results reveal the fragil...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38223-z |
| _version_ | 1797836339798867968 |
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| author | Wei Yang Li-Bo Liu Feng-Liang Liu Yan-Hua Wu Zi-Da Zhen Dong-Ying Fan Zi-Yang Sheng Zheng-Ran Song Jia-Tong Chang Yong-Tang Zheng Jing An Pei-Gang Wang |
| author_facet | Wei Yang Li-Bo Liu Feng-Liang Liu Yan-Hua Wu Zi-Da Zhen Dong-Ying Fan Zi-Yang Sheng Zheng-Ran Song Jia-Tong Chang Yong-Tang Zheng Jing An Pei-Gang Wang |
| author_sort | Wei Yang |
| collection | DOAJ |
| description | Abstract Zika virus (ZIKV) is a potential threat to male reproductive health but the mechanisms underlying its influence on testes during ZIKV infection remain obscure. To address this question, we perform single-cell RNA sequencing using testes from ZIKV-infected mice. The results reveal the fragility of spermatogenic cells, especially spermatogonia, to ZIKV infection and show that the genes of the complement system are significantly upregulated mainly in infiltrated S100A4 + monocytes/macrophages. Complement activation and its contribution to testicular damage are validated by ELISA, RT‒qPCR and IFA and further verify in ZIKV-infected northern pigtailed macaques by RNA genome sequencing and IFA, suggesting that this might be the common response to ZIKV infection in primates. On this basis, we test the complement inhibitor C1INH and S100A4 inhibitors sulindac and niclosamide for their effects on testis protection. C1INH alleviates the pathological change in the testis but deteriorates ZIKV infection in general. In contrast, niclosamide effectively reduces S100A4 + monocyte/macrophage infiltration, inhibits complement activation, alleviates testicular damage, and rescues the fertility of male mice from ZIKV infection. This discovery therefore encourages male reproductive health protection during the next ZIKV epidemic. |
| first_indexed | 2024-04-09T15:08:21Z |
| format | Article |
| id | doaj.art-3c4f912680a4472e8b5f20a294f85fab |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T15:08:21Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-3c4f912680a4472e8b5f20a294f85fab2023-04-30T11:21:10ZengNature PortfolioNature Communications2041-17232023-04-0114111710.1038/s41467-023-38223-zSingle-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activationWei Yang0Li-Bo Liu1Feng-Liang Liu2Yan-Hua Wu3Zi-Da Zhen4Dong-Ying Fan5Zi-Yang Sheng6Zheng-Ran Song7Jia-Tong Chang8Yong-Tang Zheng9Jing An10Pei-Gang Wang11Department of Microbiology, School of Basic Medical Sciences, Capital Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical UniversityKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of SciencesDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical UniversityKey Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of SciencesDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical UniversityDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical UniversityAbstract Zika virus (ZIKV) is a potential threat to male reproductive health but the mechanisms underlying its influence on testes during ZIKV infection remain obscure. To address this question, we perform single-cell RNA sequencing using testes from ZIKV-infected mice. The results reveal the fragility of spermatogenic cells, especially spermatogonia, to ZIKV infection and show that the genes of the complement system are significantly upregulated mainly in infiltrated S100A4 + monocytes/macrophages. Complement activation and its contribution to testicular damage are validated by ELISA, RT‒qPCR and IFA and further verify in ZIKV-infected northern pigtailed macaques by RNA genome sequencing and IFA, suggesting that this might be the common response to ZIKV infection in primates. On this basis, we test the complement inhibitor C1INH and S100A4 inhibitors sulindac and niclosamide for their effects on testis protection. C1INH alleviates the pathological change in the testis but deteriorates ZIKV infection in general. In contrast, niclosamide effectively reduces S100A4 + monocyte/macrophage infiltration, inhibits complement activation, alleviates testicular damage, and rescues the fertility of male mice from ZIKV infection. This discovery therefore encourages male reproductive health protection during the next ZIKV epidemic.https://doi.org/10.1038/s41467-023-38223-z |
| spellingShingle | Wei Yang Li-Bo Liu Feng-Liang Liu Yan-Hua Wu Zi-Da Zhen Dong-Ying Fan Zi-Yang Sheng Zheng-Ran Song Jia-Tong Chang Yong-Tang Zheng Jing An Pei-Gang Wang Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation Nature Communications |
| title | Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation |
| title_full | Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation |
| title_fullStr | Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation |
| title_full_unstemmed | Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation |
| title_short | Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation |
| title_sort | single cell rna sequencing reveals the fragility of male spermatogenic cells to zika virus induced complement activation |
| url | https://doi.org/10.1038/s41467-023-38223-z |
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