Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction
Nef is a multifunctional viral protein that has the ability to downregulate cell surface molecules, including CD4 and major histocompatibility complex class I (MHC-I) and, as recently shown, also members of the serine incorporator family (SERINC). Here, we analyzed the impact of naturally occurring...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/13/3/423 |
| _version_ | 1797413151735545856 |
|---|---|
| author | Zita Kruize Ad C. van Nuenen Stan W. van Wijk Arginell F. Girigorie Karel A. van Dort Thijs Booiman Neeltje A. Kootstra |
| author_facet | Zita Kruize Ad C. van Nuenen Stan W. van Wijk Arginell F. Girigorie Karel A. van Dort Thijs Booiman Neeltje A. Kootstra |
| author_sort | Zita Kruize |
| collection | DOAJ |
| description | Nef is a multifunctional viral protein that has the ability to downregulate cell surface molecules, including CD4 and major histocompatibility complex class I (MHC-I) and, as recently shown, also members of the serine incorporator family (SERINC). Here, we analyzed the impact of naturally occurring mutations in HIV-1 Nef on its ability to counteract SERINC restriction and the clinical course of infection. HIV-1 Nef sequences were obtained from 123 participants of the Amsterdam Cohort Studies and showed multiple amino acid variations and mutations. Most of the primary Nef proteins showed increased activity to counteract SERINC3 and SERINC5 as compared to NL4-3 Nef. Several mutations in Nef were associated with either an increased or decreased infectivity of Bal26-pseudotyped HIV-1 produced in the presence of SERINC3 or SERINC5. The 8R, 157N and R178G Nef mutations were shown to have an effect on disease progression. Survival analysis showed an accelerated disease progression of individuals infected with HIV-1 carrying arginine or asparagine at position 8 or 157 in Nef, respectively, or the R178G Nef mutation. Here, we observed that naturally occurring mutations in Nef affect the ability of Nef to counteract SERINC3- and SERINC5-mediated inhibition of viral infectivity. The majority of these Nef mutations had no significant effect on HIV-1 pathogenesis and only the 8R, 157N and R178G mutations were associated with disease course. |
| first_indexed | 2024-03-09T05:13:29Z |
| format | Article |
| id | doaj.art-d9addb0636644bda8fd7da4b09037f9c |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T05:13:29Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-d9addb0636644bda8fd7da4b09037f9c2023-12-03T12:47:58ZengMDPI AGViruses1999-49152021-03-0113342310.3390/v13030423Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 RestrictionZita Kruize0Ad C. van Nuenen1Stan W. van Wijk2Arginell F. Girigorie3Karel A. van Dort4Thijs Booiman5Neeltje A. Kootstra6Department of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsNef is a multifunctional viral protein that has the ability to downregulate cell surface molecules, including CD4 and major histocompatibility complex class I (MHC-I) and, as recently shown, also members of the serine incorporator family (SERINC). Here, we analyzed the impact of naturally occurring mutations in HIV-1 Nef on its ability to counteract SERINC restriction and the clinical course of infection. HIV-1 Nef sequences were obtained from 123 participants of the Amsterdam Cohort Studies and showed multiple amino acid variations and mutations. Most of the primary Nef proteins showed increased activity to counteract SERINC3 and SERINC5 as compared to NL4-3 Nef. Several mutations in Nef were associated with either an increased or decreased infectivity of Bal26-pseudotyped HIV-1 produced in the presence of SERINC3 or SERINC5. The 8R, 157N and R178G Nef mutations were shown to have an effect on disease progression. Survival analysis showed an accelerated disease progression of individuals infected with HIV-1 carrying arginine or asparagine at position 8 or 157 in Nef, respectively, or the R178G Nef mutation. Here, we observed that naturally occurring mutations in Nef affect the ability of Nef to counteract SERINC3- and SERINC5-mediated inhibition of viral infectivity. The majority of these Nef mutations had no significant effect on HIV-1 pathogenesis and only the 8R, 157N and R178G mutations were associated with disease course.https://www.mdpi.com/1999-4915/13/3/423HIV-1NefSERINC3SERINC5amino acid variationsnaturally occurring mutations |
| spellingShingle | Zita Kruize Ad C. van Nuenen Stan W. van Wijk Arginell F. Girigorie Karel A. van Dort Thijs Booiman Neeltje A. Kootstra Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction Viruses HIV-1 Nef SERINC3 SERINC5 amino acid variations naturally occurring mutations |
| title | Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction |
| title_full | Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction |
| title_fullStr | Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction |
| title_full_unstemmed | Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction |
| title_short | Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction |
| title_sort | nef obtained from individuals with hiv 1 vary in their ability to antagonize serinc3 and serinc5 mediated hiv 1 restriction |
| topic | HIV-1 Nef SERINC3 SERINC5 amino acid variations naturally occurring mutations |
| url | https://www.mdpi.com/1999-4915/13/3/423 |
| work_keys_str_mv | AT zitakruize nefobtainedfromindividualswithhiv1varyintheirabilitytoantagonizeserinc3andserinc5mediatedhiv1restriction AT adcvannuenen nefobtainedfromindividualswithhiv1varyintheirabilitytoantagonizeserinc3andserinc5mediatedhiv1restriction AT stanwvanwijk nefobtainedfromindividualswithhiv1varyintheirabilitytoantagonizeserinc3andserinc5mediatedhiv1restriction AT arginellfgirigorie nefobtainedfromindividualswithhiv1varyintheirabilitytoantagonizeserinc3andserinc5mediatedhiv1restriction AT karelavandort nefobtainedfromindividualswithhiv1varyintheirabilitytoantagonizeserinc3andserinc5mediatedhiv1restriction AT thijsbooiman nefobtainedfromindividualswithhiv1varyintheirabilitytoantagonizeserinc3andserinc5mediatedhiv1restriction AT neeltjeakootstra nefobtainedfromindividualswithhiv1varyintheirabilitytoantagonizeserinc3andserinc5mediatedhiv1restriction |