BET Inhibitor JQ1 Attenuates Feline Leukemia Virus DNA, Provirus, and Antigen Production in Domestic Cat Cell Lines
Feline leukemia virus (FeLV) is a cosmopolitan gammaretrovirus that causes lifelong infections and fatal diseases, including leukemias, lymphomas, immunodeficiencies, and anemias, in domestic and wild felids. There is currently no definitive treatment for FeLV, and while existing vaccines reduce the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/9/1853 |
| _version_ | 1797576396940247040 |
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| author | Garrick M. Moll Cheryl L. Swenson Vilma Yuzbasiyan-Gurkan |
| author_facet | Garrick M. Moll Cheryl L. Swenson Vilma Yuzbasiyan-Gurkan |
| author_sort | Garrick M. Moll |
| collection | DOAJ |
| description | Feline leukemia virus (FeLV) is a cosmopolitan gammaretrovirus that causes lifelong infections and fatal diseases, including leukemias, lymphomas, immunodeficiencies, and anemias, in domestic and wild felids. There is currently no definitive treatment for FeLV, and while existing vaccines reduce the prevalence of progressive infections, they neither provide sterilizing immunity nor prevent regressive infections that result in viral reservoirs with the potential for reactivation, transmission, and the development of associated clinical diseases. Previous studies of murine leukemia virus (MuLV) established that host cell epigenetic reader bromodomain and extra-terminal domain (BET) proteins facilitate MuLV replication by promoting proviral integration. Here, we provide evidence that this facilitatory effect of BET proteins extends to FeLV. Treatment with the archetypal BET protein bromodomain inhibitor (+)-JQ1 and FeLV challenge of two phenotypically disparate feline cell lines, 81C fibroblasts and 3201 lymphoma cells, significantly reduced FeLV proviral load, total FeLV DNA load, and p27 capsid protein expression at nonlethal concentrations. Moreover, significant decreases in FeLV proviral integration were documented in 81C and 3201 cells. These findings elucidate the importance of BET proteins for efficient FeLV replication, including proviral integration, and provide a potential target for treating FeLV infections. |
| first_indexed | 2024-03-10T21:51:32Z |
| format | Article |
| id | doaj.art-75297dddc5aa41e59acdc9556eb7e2e3 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T21:51:32Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-75297dddc5aa41e59acdc9556eb7e2e32023-11-19T13:22:38ZengMDPI AGViruses1999-49152023-08-01159185310.3390/v15091853BET Inhibitor JQ1 Attenuates Feline Leukemia Virus DNA, Provirus, and Antigen Production in Domestic Cat Cell LinesGarrick M. Moll0Cheryl L. Swenson1Vilma Yuzbasiyan-Gurkan2Comparative Medicine & Integrative Biology, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USAComparative Medicine & Integrative Biology, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USAComparative Medicine & Integrative Biology, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USAFeline leukemia virus (FeLV) is a cosmopolitan gammaretrovirus that causes lifelong infections and fatal diseases, including leukemias, lymphomas, immunodeficiencies, and anemias, in domestic and wild felids. There is currently no definitive treatment for FeLV, and while existing vaccines reduce the prevalence of progressive infections, they neither provide sterilizing immunity nor prevent regressive infections that result in viral reservoirs with the potential for reactivation, transmission, and the development of associated clinical diseases. Previous studies of murine leukemia virus (MuLV) established that host cell epigenetic reader bromodomain and extra-terminal domain (BET) proteins facilitate MuLV replication by promoting proviral integration. Here, we provide evidence that this facilitatory effect of BET proteins extends to FeLV. Treatment with the archetypal BET protein bromodomain inhibitor (+)-JQ1 and FeLV challenge of two phenotypically disparate feline cell lines, 81C fibroblasts and 3201 lymphoma cells, significantly reduced FeLV proviral load, total FeLV DNA load, and p27 capsid protein expression at nonlethal concentrations. Moreover, significant decreases in FeLV proviral integration were documented in 81C and 3201 cells. These findings elucidate the importance of BET proteins for efficient FeLV replication, including proviral integration, and provide a potential target for treating FeLV infections.https://www.mdpi.com/1999-4915/15/9/1853feline leukemia virusretrovirusgammaretrovirusesprovirusviral loadintegration |
| spellingShingle | Garrick M. Moll Cheryl L. Swenson Vilma Yuzbasiyan-Gurkan BET Inhibitor JQ1 Attenuates Feline Leukemia Virus DNA, Provirus, and Antigen Production in Domestic Cat Cell Lines Viruses feline leukemia virus retrovirus gammaretroviruses provirus viral load integration |
| title | BET Inhibitor JQ1 Attenuates Feline Leukemia Virus DNA, Provirus, and Antigen Production in Domestic Cat Cell Lines |
| title_full | BET Inhibitor JQ1 Attenuates Feline Leukemia Virus DNA, Provirus, and Antigen Production in Domestic Cat Cell Lines |
| title_fullStr | BET Inhibitor JQ1 Attenuates Feline Leukemia Virus DNA, Provirus, and Antigen Production in Domestic Cat Cell Lines |
| title_full_unstemmed | BET Inhibitor JQ1 Attenuates Feline Leukemia Virus DNA, Provirus, and Antigen Production in Domestic Cat Cell Lines |
| title_short | BET Inhibitor JQ1 Attenuates Feline Leukemia Virus DNA, Provirus, and Antigen Production in Domestic Cat Cell Lines |
| title_sort | bet inhibitor jq1 attenuates feline leukemia virus dna provirus and antigen production in domestic cat cell lines |
| topic | feline leukemia virus retrovirus gammaretroviruses provirus viral load integration |
| url | https://www.mdpi.com/1999-4915/15/9/1853 |
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