HIV-1 subtype C Nef-mediated SERINC5 down-regulation significantly contributes to overall Nef activity.
HIV-1 Nef
HIV-1 subtype C
SERINC5 down-regulation
Journal
Retrovirology
ISSN: 1742-4690
Titre abrégé: Retrovirology
Pays: England
ID NLM: 101216893
Informations de publication
Date de publication:
31 03 2023
31 03 2023
Historique:
received:
10
02
2023
accepted:
10
03
2023
medline:
4
4
2023
entrez:
2
4
2023
pubmed:
3
4
2023
Statut:
epublish
Résumé
Nef performs multiple cellular activities that enhance HIV-1 pathogenesis. The role of Nef-mediated down-regulation of the host restriction factor SERINC5 in HIV-1 pathogenesis is not well-defined. We aimed to investigate if SERINC5 down-regulation activity contributes to HIV-1 subtype C disease progression, to assess the relative contribution of this activity to overall Nef function, and to identify amino acids required for optimal activity. We measured the SERINC5 down-regulation activity of 106 subtype C Nef clones, isolated from individuals in early infection, for which the Nef activities of CD4 and HLA-I down-regulation as well as alteration of TCR signalling were previously measured. The relationship between SERINC5 down-regulation and markers of disease progression, and the relative contribution of SERINC5 down-regulation to a Nef fitness model-derived E value (a proxy for overall Nef fitness in vivo), were assessed. No overall relationship was found between SERINC5 down-regulation and viral load set point (p = 0.28) or rate of CD4 These results suggest that SERINC5 down-regulation is a significant contributor to overall Nef function and identify potential genetic determinants of this Nef function that may have relevance for vaccines or therapeutics.
Sections du résumé
BACKGROUND
Nef performs multiple cellular activities that enhance HIV-1 pathogenesis. The role of Nef-mediated down-regulation of the host restriction factor SERINC5 in HIV-1 pathogenesis is not well-defined. We aimed to investigate if SERINC5 down-regulation activity contributes to HIV-1 subtype C disease progression, to assess the relative contribution of this activity to overall Nef function, and to identify amino acids required for optimal activity. We measured the SERINC5 down-regulation activity of 106 subtype C Nef clones, isolated from individuals in early infection, for which the Nef activities of CD4 and HLA-I down-regulation as well as alteration of TCR signalling were previously measured. The relationship between SERINC5 down-regulation and markers of disease progression, and the relative contribution of SERINC5 down-regulation to a Nef fitness model-derived E value (a proxy for overall Nef fitness in vivo), were assessed.
RESULTS
No overall relationship was found between SERINC5 down-regulation and viral load set point (p = 0.28) or rate of CD4
CONCLUSIONS
These results suggest that SERINC5 down-regulation is a significant contributor to overall Nef function and identify potential genetic determinants of this Nef function that may have relevance for vaccines or therapeutics.
Identifiants
pubmed: 37004071
doi: 10.1186/s12977-023-00618-7
pii: 10.1186/s12977-023-00618-7
pmc: PMC10067162
doi:
Substances chimiques
Membrane Proteins
0
nef Gene Products, Human Immunodeficiency Virus
0
nef protein, Human immunodeficiency virus 2
0
nef protein, Human immunodeficiency virus 1
0
SERINC5 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3Subventions
Organisme : Wellcome Trust
ID : 107752/Z/15/Z
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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