Unknown

Dataset Information

0

A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells.


ABSTRACT: Dendritic cells serve a key function in host defence, linking innate detection of microbes to activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of human immunodeficiency virus (HIV) by host innate pattern-recognition receptors and subsequent coupling to antiviral T-cell responses is not yet known. Dendritic cells are largely resistant to infection with HIV-1, but facilitate infection of co-cultured T-helper cells through a process of trans-enhancement. Here we show that, when dendritic cell resistance to infection is circumvented, HIV-1 induces dendritic cell maturation, an antiviral type I interferon response and activation of T cells. This innate response is dependent on the interaction of newly synthesized HIV-1 capsid with cellular cyclophilin A (CYPA) and the subsequent activation of the transcription factor IRF3. Because the peptidylprolyl isomerase CYPA also interacts with HIV-1 capsid to promote infectivity, our results indicate that capsid conformation has evolved under opposing selective pressures for infectivity versus furtiveness. Thus, a cell-intrinsic sensor for HIV-1 exists in dendritic cells and mediates an antiviral immune response, but it is not typically engaged owing to the absence of dendritic cell infection. The virulence of HIV-1 may be related to evasion of this response, the manipulation of which may be necessary to generate an effective HIV-1 vaccine.

SUBMITTER: Manel N 

PROVIDER: S-EPMC3051279 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells.

Manel Nicolas N   Hogstad Brandon B   Wang Yaming Y   Levy David E DE   Unutmaz Derya D   Littman Dan R DR  

Nature 20100901 7312


Dendritic cells serve a key function in host defence, linking innate detection of microbes to activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of human immunodeficiency virus (HIV) by host innate pattern-recognition receptors and subsequent coupling to antiviral T-cell responses is not yet known. Dendritic cells are largely resistant to infection with HIV-1, but facilitate infection of co-cultured T-helper cells through a process of trans-enh  ...[more]

Similar Datasets

2010-09-09 | E-GEOD-22589 | biostudies-arrayexpress
2010-09-09 | GSE22589 | GEO
| S-EPMC5662903 | biostudies-literature
2017-09-26 | GSE104236 | GEO
| S-EPMC4927078 | biostudies-other
| S-EPMC3148698 | biostudies-literature
| S-EPMC4156907 | biostudies-literature
| S-EPMC434082 | biostudies-other
| S-EPMC4874888 | biostudies-other
| S-SCDT-10_15252-EMBJ_2022113258 | biostudies-other