Characterization of the Effects of Host p53 and Fos on Gallid Alpha Herpesvirus 1 Replication
Treatment options for herpesvirus infections that target the interactions between the virus and the host have been identified as promising. Our previous studies have shown that transcription factors p53 and Fos are essential host determinants of gallid alpha herpesvirus 1 (ILTV) infection. The impac...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/14/8/1615 |
| _version_ | 1797584609331904512 |
|---|---|
| author | Zheyi Liu Lu Cui Xuefeng Li Li Xu Yu Zhang Zongxi Han Shengwang Liu Hai Li |
| author_facet | Zheyi Liu Lu Cui Xuefeng Li Li Xu Yu Zhang Zongxi Han Shengwang Liu Hai Li |
| author_sort | Zheyi Liu |
| collection | DOAJ |
| description | Treatment options for herpesvirus infections that target the interactions between the virus and the host have been identified as promising. Our previous studies have shown that transcription factors p53 and Fos are essential host determinants of gallid alpha herpesvirus 1 (ILTV) infection. The impact of p53 and Fos on ILTV replication has ‘not been fully understood yet. Using the sole ILTV-permissive chicken cell line LMH as a model, we examined the effects of hosts p53 and Fos on all phases of ILTV replication, including viral gene transcription, viral genome replication, and infectious virion generation. We achieved this by manipulating the expression of p53 and Fos in LMH cells. Our results demonstrate that the overexpression of either p53 or Fos can promote viral gene transcription at all stages of the temporal cascade of ILTV gene expression, viral genome replication, and infectious virion production, as assessed through absolute quantitative real-time PCR, ILTV-specific RT-qPCR assays, and TCID<sub>50</sub> assays. These findings are consistent with our previous analyses of the effects of Fos and p53 knockdowns on virus production and also suggest that both p53 and Fos may be dispensable for ILTV replication. Based on the synergistic effect of regulating ILTV, we further found that there is an interaction between p53 and Fos. Interestingly, we found that p53 also has targeted sites upstream of <i>ICP4</i>, and these sites are very close to the Fos sites. In conclusion, our research offers an in-depth understanding of how hosts p53 and Fos affect ILTV replication. Understanding the processes by which p53 and Fos regulate ILTV infection will be improved by this knowledge, potentially paving the way for the development of novel therapeutics targeting virus–host interactions as a means of treating herpesvirus infections. |
| first_indexed | 2024-03-10T23:54:04Z |
| format | Article |
| id | doaj.art-29acf191df414eb58b2e4a4d352127aa |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T23:54:04Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-29acf191df414eb58b2e4a4d352127aa2023-11-19T01:15:57ZengMDPI AGGenes2073-44252023-08-01148161510.3390/genes14081615Characterization of the Effects of Host p53 and Fos on Gallid Alpha Herpesvirus 1 ReplicationZheyi Liu0Lu Cui1Xuefeng Li2Li Xu3Yu Zhang4Zongxi Han5Shengwang Liu6Hai Li7Division of Avian Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, National Poultry Laboratory Animal Resource Center, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaDivision of Avian Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, National Poultry Laboratory Animal Resource Center, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaDivision of Avian Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, National Poultry Laboratory Animal Resource Center, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaDivision of Avian Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, National Poultry Laboratory Animal Resource Center, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaDivision of Avian Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, National Poultry Laboratory Animal Resource Center, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaDivision of Avian Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, National Poultry Laboratory Animal Resource Center, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaDivision of Avian Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, National Poultry Laboratory Animal Resource Center, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, ChinaDepartment of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an 710061, ChinaTreatment options for herpesvirus infections that target the interactions between the virus and the host have been identified as promising. Our previous studies have shown that transcription factors p53 and Fos are essential host determinants of gallid alpha herpesvirus 1 (ILTV) infection. The impact of p53 and Fos on ILTV replication has ‘not been fully understood yet. Using the sole ILTV-permissive chicken cell line LMH as a model, we examined the effects of hosts p53 and Fos on all phases of ILTV replication, including viral gene transcription, viral genome replication, and infectious virion generation. We achieved this by manipulating the expression of p53 and Fos in LMH cells. Our results demonstrate that the overexpression of either p53 or Fos can promote viral gene transcription at all stages of the temporal cascade of ILTV gene expression, viral genome replication, and infectious virion production, as assessed through absolute quantitative real-time PCR, ILTV-specific RT-qPCR assays, and TCID<sub>50</sub> assays. These findings are consistent with our previous analyses of the effects of Fos and p53 knockdowns on virus production and also suggest that both p53 and Fos may be dispensable for ILTV replication. Based on the synergistic effect of regulating ILTV, we further found that there is an interaction between p53 and Fos. Interestingly, we found that p53 also has targeted sites upstream of <i>ICP4</i>, and these sites are very close to the Fos sites. In conclusion, our research offers an in-depth understanding of how hosts p53 and Fos affect ILTV replication. Understanding the processes by which p53 and Fos regulate ILTV infection will be improved by this knowledge, potentially paving the way for the development of novel therapeutics targeting virus–host interactions as a means of treating herpesvirus infections.https://www.mdpi.com/2073-4425/14/8/1615alphaherpesvirusesp53Fosvirus–host interactionsvirus replication |
| spellingShingle | Zheyi Liu Lu Cui Xuefeng Li Li Xu Yu Zhang Zongxi Han Shengwang Liu Hai Li Characterization of the Effects of Host p53 and Fos on Gallid Alpha Herpesvirus 1 Replication Genes alphaherpesviruses p53 Fos virus–host interactions virus replication |
| title | Characterization of the Effects of Host p53 and Fos on Gallid Alpha Herpesvirus 1 Replication |
| title_full | Characterization of the Effects of Host p53 and Fos on Gallid Alpha Herpesvirus 1 Replication |
| title_fullStr | Characterization of the Effects of Host p53 and Fos on Gallid Alpha Herpesvirus 1 Replication |
| title_full_unstemmed | Characterization of the Effects of Host p53 and Fos on Gallid Alpha Herpesvirus 1 Replication |
| title_short | Characterization of the Effects of Host p53 and Fos on Gallid Alpha Herpesvirus 1 Replication |
| title_sort | characterization of the effects of host p53 and fos on gallid alpha herpesvirus 1 replication |
| topic | alphaherpesviruses p53 Fos virus–host interactions virus replication |
| url | https://www.mdpi.com/2073-4425/14/8/1615 |
| work_keys_str_mv | AT zheyiliu characterizationoftheeffectsofhostp53andfosongallidalphaherpesvirus1replication AT lucui characterizationoftheeffectsofhostp53andfosongallidalphaherpesvirus1replication AT xuefengli characterizationoftheeffectsofhostp53andfosongallidalphaherpesvirus1replication AT lixu characterizationoftheeffectsofhostp53andfosongallidalphaherpesvirus1replication AT yuzhang characterizationoftheeffectsofhostp53andfosongallidalphaherpesvirus1replication AT zongxihan characterizationoftheeffectsofhostp53andfosongallidalphaherpesvirus1replication AT shengwangliu characterizationoftheeffectsofhostp53andfosongallidalphaherpesvirus1replication AT haili characterizationoftheeffectsofhostp53andfosongallidalphaherpesvirus1replication |