Cargando…
Ceramide synthase 2 deletion decreases the infectivity of HIV-1
The lipid composition of HIV-1 virions is enriched in sphingomyelin (SM), but the roles that SM or other sphingolipids (SLs) might play in the HIV-1 replication pathway have not been elucidated. In human cells, SL levels are regulated by ceramide synthase (CerS) enzymes that produce ceramides, which...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949126/ https://www.ncbi.nlm.nih.gov/pubmed/33515546 http://dx.doi.org/10.1016/j.jbc.2021.100340 |
_version_ | 1783663495988903936 |
---|---|
author | Barklis, Eric Alfadhli, Ayna Kyle, Jennifer E. Bramer, Lisa M. Bloodsworth, Kent J. Barklis, Robin Lid Leier, Hans C. Petty, R. Max Zelnik, Iris D. Metz, Thomas O. Futerman, Anthony H. Tafesse, Fikadu G. |
author_facet | Barklis, Eric Alfadhli, Ayna Kyle, Jennifer E. Bramer, Lisa M. Bloodsworth, Kent J. Barklis, Robin Lid Leier, Hans C. Petty, R. Max Zelnik, Iris D. Metz, Thomas O. Futerman, Anthony H. Tafesse, Fikadu G. |
author_sort | Barklis, Eric |
collection | PubMed |
description | The lipid composition of HIV-1 virions is enriched in sphingomyelin (SM), but the roles that SM or other sphingolipids (SLs) might play in the HIV-1 replication pathway have not been elucidated. In human cells, SL levels are regulated by ceramide synthase (CerS) enzymes that produce ceramides, which can be converted to SMs, hexosylceramides, and other SLs. In many cell types, CerS2, which catalyzes the synthesis of very long chain ceramides, is the major CerS. We have examined how CerS2 deficiency affects the assembly and infectivity of HIV-1. As expected, we observed that very long chain ceramide, hexosylceramide, and SM were reduced in CerS2 knockout cells. CerS2 deficiency did not affect HIV-1 assembly or the incorporation of the HIV-1 envelope (Env) protein into virus particles, but it reduced the infectivites of viruses produced in the CerS2-deficient cells. The reduced viral infection levels were dependent on HIV-1 Env, since HIV-1 particles that were pseudotyped with the vesicular stomatitis virus glycoprotein did not exhibit reductions in infectivity. Moreover, cell–cell fusion assays demonstrated that the functional defect of HIV-1 Env in CerS2-deficient cells was independent of other viral proteins. Overall, our results indicate that the altered lipid composition of CerS2-deficient cells specifically inhibit the HIV-1 Env receptor binding and/or fusion processes. |
format | Online Article Text |
id | pubmed-7949126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-79491262021-03-19 Ceramide synthase 2 deletion decreases the infectivity of HIV-1 Barklis, Eric Alfadhli, Ayna Kyle, Jennifer E. Bramer, Lisa M. Bloodsworth, Kent J. Barklis, Robin Lid Leier, Hans C. Petty, R. Max Zelnik, Iris D. Metz, Thomas O. Futerman, Anthony H. Tafesse, Fikadu G. J Biol Chem Research Article The lipid composition of HIV-1 virions is enriched in sphingomyelin (SM), but the roles that SM or other sphingolipids (SLs) might play in the HIV-1 replication pathway have not been elucidated. In human cells, SL levels are regulated by ceramide synthase (CerS) enzymes that produce ceramides, which can be converted to SMs, hexosylceramides, and other SLs. In many cell types, CerS2, which catalyzes the synthesis of very long chain ceramides, is the major CerS. We have examined how CerS2 deficiency affects the assembly and infectivity of HIV-1. As expected, we observed that very long chain ceramide, hexosylceramide, and SM were reduced in CerS2 knockout cells. CerS2 deficiency did not affect HIV-1 assembly or the incorporation of the HIV-1 envelope (Env) protein into virus particles, but it reduced the infectivites of viruses produced in the CerS2-deficient cells. The reduced viral infection levels were dependent on HIV-1 Env, since HIV-1 particles that were pseudotyped with the vesicular stomatitis virus glycoprotein did not exhibit reductions in infectivity. Moreover, cell–cell fusion assays demonstrated that the functional defect of HIV-1 Env in CerS2-deficient cells was independent of other viral proteins. Overall, our results indicate that the altered lipid composition of CerS2-deficient cells specifically inhibit the HIV-1 Env receptor binding and/or fusion processes. American Society for Biochemistry and Molecular Biology 2021-01-28 /pmc/articles/PMC7949126/ /pubmed/33515546 http://dx.doi.org/10.1016/j.jbc.2021.100340 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Barklis, Eric Alfadhli, Ayna Kyle, Jennifer E. Bramer, Lisa M. Bloodsworth, Kent J. Barklis, Robin Lid Leier, Hans C. Petty, R. Max Zelnik, Iris D. Metz, Thomas O. Futerman, Anthony H. Tafesse, Fikadu G. Ceramide synthase 2 deletion decreases the infectivity of HIV-1 |
title | Ceramide synthase 2 deletion decreases the infectivity of HIV-1 |
title_full | Ceramide synthase 2 deletion decreases the infectivity of HIV-1 |
title_fullStr | Ceramide synthase 2 deletion decreases the infectivity of HIV-1 |
title_full_unstemmed | Ceramide synthase 2 deletion decreases the infectivity of HIV-1 |
title_short | Ceramide synthase 2 deletion decreases the infectivity of HIV-1 |
title_sort | ceramide synthase 2 deletion decreases the infectivity of hiv-1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949126/ https://www.ncbi.nlm.nih.gov/pubmed/33515546 http://dx.doi.org/10.1016/j.jbc.2021.100340 |
work_keys_str_mv | AT barkliseric ceramidesynthase2deletiondecreasestheinfectivityofhiv1 AT alfadhliayna ceramidesynthase2deletiondecreasestheinfectivityofhiv1 AT kylejennifere ceramidesynthase2deletiondecreasestheinfectivityofhiv1 AT bramerlisam ceramidesynthase2deletiondecreasestheinfectivityofhiv1 AT bloodsworthkentj ceramidesynthase2deletiondecreasestheinfectivityofhiv1 AT barklisrobinlid ceramidesynthase2deletiondecreasestheinfectivityofhiv1 AT leierhansc ceramidesynthase2deletiondecreasestheinfectivityofhiv1 AT pettyrmax ceramidesynthase2deletiondecreasestheinfectivityofhiv1 AT zelnikirisd ceramidesynthase2deletiondecreasestheinfectivityofhiv1 AT metzthomaso ceramidesynthase2deletiondecreasestheinfectivityofhiv1 AT futermananthonyh ceramidesynthase2deletiondecreasestheinfectivityofhiv1 AT tafessefikadug ceramidesynthase2deletiondecreasestheinfectivityofhiv1 |