SERINC5 Is an Unconventional HIV Restriction Factor That Is Upregulated during Myeloid Cell Differentiation.
CD4-Positive T-Lymphocytes
/ cytology
Cell Differentiation
Cytokines
/ pharmacology
HIV Infections
/ immunology
HIV-1
/ genetics
Humans
Immunity, Innate
Macrophages
/ cytology
Membrane Glycoproteins
/ genetics
Membrane Proteins
/ genetics
Monocytes
/ cytology
Myeloid Cells
/ cytology
RNA, Messenger
/ metabolism
Virus Replication
nef Gene Products, Human Immunodeficiency Virus
/ genetics
Adaptive immunity
HIV
Innate restriction factor
Myeloid cell differentiation
SERINC5
Journal
Journal of innate immunity
ISSN: 1662-8128
Titre abrégé: J Innate Immun
Pays: Switzerland
ID NLM: 101469471
Informations de publication
Date de publication:
2020
2020
Historique:
received:
12
08
2019
accepted:
15
11
2019
pubmed:
15
1
2020
medline:
17
7
2021
entrez:
15
1
2020
Statut:
ppublish
Résumé
Classical antiviral restriction factors promote cellular immunity by their ability to interfere with virus replication and induction of their expression by proinflammatory cytokines such as interferons. The serine incorporator proteins SERINC3 and SERINC5 potently reduce the infectivity of HIV-1 particles when overexpressed, and RNA interference or knockout approaches in T cells have indicated antiviral activity also of the endogenous proteins. Due to lack of reagents for detection of endogenous SERINC proteins, it is still unclear whether SERINC3/5 are expressed to functionally relevant levels in different primary target cells of HIV infection and how the expression levels of these innate immunity factors are regulated. In the current study, analysis of SERINC3/5 mRNA steady-state levels in primary lymphoid and monocyte-derived cells revealed selective induction of their expression upon differentiation of myeloid cells. Contrary to classical antiviral restriction factors, various antiviral α-interferon subtypes and proinflammatory interleukins had no effect on SERINC levels, which were also not dysregulated in CD4+ T cells and monocytes isolated from patients with chronic HIV-1 infection. Notably, HIV-1 particles produced by terminally differentiated monocyte-derived macrophages with high SERINC5 expression, but not by low-expressing monocytes, showed a Nef-dependent infectivity defect. Overall, these findings suggest endogenous expression of SERINC5 to antivirally active levels in macrophages. Our results classify SERINC5 as an unconventional HIV-1 restriction factor whose expression is specifically induced upon differentiation of cells towards the myeloid lineage.
Identifiants
pubmed: 31935717
pii: 000504888
doi: 10.1159/000504888
pmc: PMC7900780
doi:
Substances chimiques
Cytokines
0
Membrane Glycoproteins
0
Membrane Proteins
0
RNA, Messenger
0
SERINC3 protein, human
0
SERINC5 protein, human
0
nef Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
399-409Informations de copyright
© 2020 The Author(s) Published by S. Karger AG, Basel.
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