Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-04

AUTHORS

Sam X Li, Bradley S Barrett, Kejun Guo, George Kassiotis, Kim J Hasenkrug, Ulf Dittmer, Kathrin Gibbert, Mario L Santiago

ABSTRACT

Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. More... »

PAGES

20425

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep20425

DOI

http://dx.doi.org/10.1038/srep20425

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022658592

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26846717


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