Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells.
PLoS Pathog
; 11(6): e1005005, 2015 Jun.
Article
en En
| MEDLINE
| ID: mdl-26121641
ABSTRACT
DCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus, DCs are productively infected only at very low levels with HIV-1, and this non-permissiveness of DCs is suggested to go along with viral evasion. We now illustrate that complement-opsonized HIV-1 (HIV-C) efficiently bypasses SAMHD1 restriction and productively infects DCs including BDCA-1 DCs. Efficient DC infection by HIV-C was also observed using single-cycle HIV-C, and correlated with a remarkable elevated SAMHD1 T592 phosphorylation but not SAMHD1 degradation. If SAMHD1 phosphorylation was blocked using a CDK2-inhibitor HIV-C-induced DC infection was also significantly abrogated. Additionally, we found a higher maturation and co-stimulatory potential, aberrant type I interferon expression and signaling as well as a stronger induction of cellular immune responses in HIV-C-treated DCs. Collectively, our data highlight a novel protective mechanism mediated by complement opsonization of HIV to effectively promote DC immune functions, which might be in the future exploited to tackle HIV infection.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Linfocitos T CD4-Positivos
/
Infecciones por VIH
/
VIH-1
Límite:
Humans
Idioma:
En
Revista:
PLoS Pathog
Año:
2015
Tipo del documento:
Article
País de afiliación:
Austria