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Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC84B on the early steps of HIV-1 infection
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| Veröffentlicht in: | Journal of virology 91(2017,19) Artikel-Nummer e00463-17, 21 Seiten |
|---|---|
| Personen und Körperschaften: | , , , |
| Titel: | Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC84B on the early steps of HIV-1 infection/ Torsten Schaller, Lorenzo Bulli, Darja Pollpeter, Gilberto Betancor, Juliane Kutzner, Luis Apolonia, Nikolas Herold, Robin Burk, Michael H. Malim |
| Format: | E-Book-Kapitel |
| Sprache: | Englisch |
| veröffentlicht: |
26 July 2017
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| Gesamtaufnahme: |
: Journal of virology, 91(2017,19) Artikel-Nummer e00463-17, 21 Seiten
, volume:91 |
| Schlagwörter: | |
| Quelle: | Verbunddaten SWB Lizenzfreie Online-Ressourcen |
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| 245 | 1 | 0 | |a Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC84B on the early steps of HIV-1 infection |c Torsten Schaller, Lorenzo Bulli, Darja Pollpeter, Gilberto Betancor, Juliane Kutzner, Luis Apolonia, Nikolas Herold, Robin Burk, Michael H. Malim |
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| 520 | |a Human immunodeficiency virus type 1 (HIV-1) infection of dividing and nondividing cells involves regulatory interactions with the nuclear pore complex (NPC), followed by translocation to the nucleus and preferential integration into genomic areas in proximity to the inner nuclear membrane (INM). To identify host proteins that may contribute to these processes, we performed an overexpression screen of known membrane-associated NE proteins. We found that the integral transmembrane proteins SUN1/UNC84A and SUN2/UNC84B are potent or modest inhibitors of HIV-1 infection, respectively, and that suppression corresponds to defects in the accumulation of viral cDNA in the nucleus. While laboratory strains (HIV-1NL4.3 and HIV-1IIIB) are sensitive to SUN1-mediated inhibition, the transmitted founder viruses RHPA and ZM247 are largely resistant. Using chimeric viruses, we identified the HIV-1 capsid (CA) protein as a major determinant of sensitivity to SUN1, and in vitro-assembled capsid-nucleocapsid (CANC) nanotubes captured SUN1 and SUN2 from cell lysates. Finally, we generated SUN1-/- and SUN2-/- cells by using CRISPR/Cas9 and found that the loss of SUN1 had no effect on HIV-1 infectivity, whereas the loss of SUN2 had a modest suppressive effect. Taken together, these observations suggest that SUN1 and SUN2 may function redundantly to modulate postentry, nuclear-associated steps of HIV-1 infection. IMPORTANCE: HIV-1 causes more than 1 million deaths per year. The life cycle of HIV-1 has been studied extensively, yet important steps that occur between viral capsid release into the cytoplasm and the expression of viral genes remain elusive. We propose here that the INM components SUN1 and SUN2, two members of the linker of nucleoskeleton and cytoskeleton (LINC) complex, may interact with incoming HIV-1 replication complexes and affect key steps of infection. While overexpression of these proteins reduces HIV-1 infection, disruption of the individual SUN2 and SUN1 genes leads to a mild reduction or no effect on infectivity, respectively. We speculate that SUN1/SUN2 may function redundantly in early HIV-1 infection steps and therefore influence HIV-1 replication and pathogenesis. | ||
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| 650 | 4 | |a cyclophilin A | |
| 650 | 4 | |a early infection | |
| 650 | 4 | |a nuclear envelope | |
| 650 | 4 | |a nuclear import | |
| 650 | 4 | |a nuclear pore complex | |
| 650 | 4 | |a transmitted founder virus | |
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| contents | Human immunodeficiency virus type 1 (HIV-1) infection of dividing and nondividing cells involves regulatory interactions with the nuclear pore complex (NPC), followed by translocation to the nucleus and preferential integration into genomic areas in proximity to the inner nuclear membrane (INM). To identify host proteins that may contribute to these processes, we performed an overexpression screen of known membrane-associated NE proteins. We found that the integral transmembrane proteins SUN1/UNC84A and SUN2/UNC84B are potent or modest inhibitors of HIV-1 infection, respectively, and that suppression corresponds to defects in the accumulation of viral cDNA in the nucleus. While laboratory strains (HIV-1NL4.3 and HIV-1IIIB) are sensitive to SUN1-mediated inhibition, the transmitted founder viruses RHPA and ZM247 are largely resistant. Using chimeric viruses, we identified the HIV-1 capsid (CA) protein as a major determinant of sensitivity to SUN1, and in vitro-assembled capsid-nucleocapsid (CANC) nanotubes captured SUN1 and SUN2 from cell lysates. Finally, we generated SUN1-/- and SUN2-/- cells by using CRISPR/Cas9 and found that the loss of SUN1 had no effect on HIV-1 infectivity, whereas the loss of SUN2 had a modest suppressive effect. Taken together, these observations suggest that SUN1 and SUN2 may function redundantly to modulate postentry, nuclear-associated steps of HIV-1 infection. IMPORTANCE: HIV-1 causes more than 1 million deaths per year. The life cycle of HIV-1 has been studied extensively, yet important steps that occur between viral capsid release into the cytoplasm and the expression of viral genes remain elusive. We propose here that the INM components SUN1 and SUN2, two members of the linker of nucleoskeleton and cytoskeleton (LINC) complex, may interact with incoming HIV-1 replication complexes and affect key steps of infection. While overexpression of these proteins reduces HIV-1 infection, disruption of the individual SUN2 and SUN1 genes leads to a mild reduction or no effect on infectivity, respectively. We speculate that SUN1/SUN2 may function redundantly in early HIV-1 infection steps and therefore influence HIV-1 replication and pathogenesis. |
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| spelling | Schaller, Torsten VerfasserIn (DE-588)1155841174 (DE-627)1018325425 (DE-576)501895574 aut, Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC84B on the early steps of HIV-1 infection Torsten Schaller, Lorenzo Bulli, Darja Pollpeter, Gilberto Betancor, Juliane Kutzner, Luis Apolonia, Nikolas Herold, Robin Burk, Michael H. Malim, 26 July 2017, 21, Text txt rdacontent, Computermedien c rdamedia, Online-Ressource cr rdacarrier, Gesehen am 28.04.2022, Human immunodeficiency virus type 1 (HIV-1) infection of dividing and nondividing cells involves regulatory interactions with the nuclear pore complex (NPC), followed by translocation to the nucleus and preferential integration into genomic areas in proximity to the inner nuclear membrane (INM). To identify host proteins that may contribute to these processes, we performed an overexpression screen of known membrane-associated NE proteins. We found that the integral transmembrane proteins SUN1/UNC84A and SUN2/UNC84B are potent or modest inhibitors of HIV-1 infection, respectively, and that suppression corresponds to defects in the accumulation of viral cDNA in the nucleus. While laboratory strains (HIV-1NL4.3 and HIV-1IIIB) are sensitive to SUN1-mediated inhibition, the transmitted founder viruses RHPA and ZM247 are largely resistant. Using chimeric viruses, we identified the HIV-1 capsid (CA) protein as a major determinant of sensitivity to SUN1, and in vitro-assembled capsid-nucleocapsid (CANC) nanotubes captured SUN1 and SUN2 from cell lysates. Finally, we generated SUN1-/- and SUN2-/- cells by using CRISPR/Cas9 and found that the loss of SUN1 had no effect on HIV-1 infectivity, whereas the loss of SUN2 had a modest suppressive effect. Taken together, these observations suggest that SUN1 and SUN2 may function redundantly to modulate postentry, nuclear-associated steps of HIV-1 infection. IMPORTANCE: HIV-1 causes more than 1 million deaths per year. The life cycle of HIV-1 has been studied extensively, yet important steps that occur between viral capsid release into the cytoplasm and the expression of viral genes remain elusive. We propose here that the INM components SUN1 and SUN2, two members of the linker of nucleoskeleton and cytoskeleton (LINC) complex, may interact with incoming HIV-1 replication complexes and affect key steps of infection. While overexpression of these proteins reduces HIV-1 infection, disruption of the individual SUN2 and SUN1 genes leads to a mild reduction or no effect on infectivity, respectively. We speculate that SUN1/SUN2 may function redundantly in early HIV-1 infection steps and therefore influence HIV-1 replication and pathogenesis., CA, HIV-1, SUN1, SUN2, cyclophilin A, early infection, nuclear envelope, nuclear import, nuclear pore complex, transmitted founder virus, Bulli, Lorenzo VerfasserIn (DE-588)115584145X (DE-627)1018325697 (DE-576)501895892 aut, Kutzner, Juliane VerfasserIn (DE-588)1155841034 (DE-627)1018325247 (DE-576)501895159 aut, Burk, Robin VerfasserIn (DE-588)1155840836 (DE-627)1018325166 (DE-576)501895191 aut, Enthalten in Journal of virology Baltimore, Md. : Soc., 1967 91(2017,19) Artikel-Nummer e00463-17, 21 Seiten Online-Ressource (DE-627)303614609 (DE-600)1495529-5 (DE-576)08088766X 1098-5514 nnns, volume:91 year:2017 number:19 extent:21, http://dx.doi.org/10.1128/JVI.00463-17 Verlag Resolving-System kostenfrei Volltext, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599759 Verlag kostenfrei Volltext, http://dx.doi.org/10.1128/JVI.00463-17 LFER, LFER 2018-05-17T00:00:00Z |
| spellingShingle | Schaller, Torsten, Bulli, Lorenzo, Kutzner, Juliane, Burk, Robin, Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC84B on the early steps of HIV-1 infection, Human immunodeficiency virus type 1 (HIV-1) infection of dividing and nondividing cells involves regulatory interactions with the nuclear pore complex (NPC), followed by translocation to the nucleus and preferential integration into genomic areas in proximity to the inner nuclear membrane (INM). To identify host proteins that may contribute to these processes, we performed an overexpression screen of known membrane-associated NE proteins. We found that the integral transmembrane proteins SUN1/UNC84A and SUN2/UNC84B are potent or modest inhibitors of HIV-1 infection, respectively, and that suppression corresponds to defects in the accumulation of viral cDNA in the nucleus. While laboratory strains (HIV-1NL4.3 and HIV-1IIIB) are sensitive to SUN1-mediated inhibition, the transmitted founder viruses RHPA and ZM247 are largely resistant. Using chimeric viruses, we identified the HIV-1 capsid (CA) protein as a major determinant of sensitivity to SUN1, and in vitro-assembled capsid-nucleocapsid (CANC) nanotubes captured SUN1 and SUN2 from cell lysates. Finally, we generated SUN1-/- and SUN2-/- cells by using CRISPR/Cas9 and found that the loss of SUN1 had no effect on HIV-1 infectivity, whereas the loss of SUN2 had a modest suppressive effect. Taken together, these observations suggest that SUN1 and SUN2 may function redundantly to modulate postentry, nuclear-associated steps of HIV-1 infection. IMPORTANCE: HIV-1 causes more than 1 million deaths per year. The life cycle of HIV-1 has been studied extensively, yet important steps that occur between viral capsid release into the cytoplasm and the expression of viral genes remain elusive. We propose here that the INM components SUN1 and SUN2, two members of the linker of nucleoskeleton and cytoskeleton (LINC) complex, may interact with incoming HIV-1 replication complexes and affect key steps of infection. While overexpression of these proteins reduces HIV-1 infection, disruption of the individual SUN2 and SUN1 genes leads to a mild reduction or no effect on infectivity, respectively. We speculate that SUN1/SUN2 may function redundantly in early HIV-1 infection steps and therefore influence HIV-1 replication and pathogenesis., CA, HIV-1, SUN1, SUN2, cyclophilin A, early infection, nuclear envelope, nuclear import, nuclear pore complex, transmitted founder virus |
| swb_id_str | 501894519 |
| title | Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC84B on the early steps of HIV-1 infection |
| title_auth | Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC84B on the early steps of HIV-1 infection |
| title_full | Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC84B on the early steps of HIV-1 infection Torsten Schaller, Lorenzo Bulli, Darja Pollpeter, Gilberto Betancor, Juliane Kutzner, Luis Apolonia, Nikolas Herold, Robin Burk, Michael H. Malim |
| title_fullStr | Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC84B on the early steps of HIV-1 infection Torsten Schaller, Lorenzo Bulli, Darja Pollpeter, Gilberto Betancor, Juliane Kutzner, Luis Apolonia, Nikolas Herold, Robin Burk, Michael H. Malim |
| title_full_unstemmed | Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC84B on the early steps of HIV-1 infection Torsten Schaller, Lorenzo Bulli, Darja Pollpeter, Gilberto Betancor, Juliane Kutzner, Luis Apolonia, Nikolas Herold, Robin Burk, Michael H. Malim |
| title_in_hierarchy | Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC84B on the early steps of HIV-1 infection / Torsten Schaller, Lorenzo Bulli, Darja Pollpeter, Gilberto Betancor, Juliane Kutzner, Luis Apolonia, Nikolas Herold, Robin Burk, Michael H. Malim, |
| title_short | Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC84B on the early steps of HIV-1 infection |
| title_sort | effects of inner nuclear membrane proteins sun1 unc 84a and sun2 unc84b on the early steps of hiv 1 infection |
| topic | CA, HIV-1, SUN1, SUN2, cyclophilin A, early infection, nuclear envelope, nuclear import, nuclear pore complex, transmitted founder virus |
| topic_facet | CA, HIV-1, SUN1, SUN2, cyclophilin A, early infection, nuclear envelope, nuclear import, nuclear pore complex, transmitted founder virus |
| url | http://dx.doi.org/10.1128/JVI.00463-17, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599759 |