Related Experiment Video
Updated: May 8, 2026
11:44
A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
Intact type I Interferon production and IRF7 function in sooty mangabeys
Steven E Bosinger1, Zachary P Johnson, Kathryn A Folkner
1Divison of Microbiology and Immunology, Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, Georgia, United States of America. sbosing@emory.edu
Plos Pathogens
|September 7, 2013
Summary
Sooty mangabeys (SMs) resist AIDS from SIV infection due to intact, not muted, interferon-alpha (IFN-α) responses. Contrary to prior beliefs, SM IRF7 and IFN-α signaling are functional, explaining their AIDS resistance.
Area of Science:
- Immunology
- Virology
- Primate Models
Background:
- Sooty mangabeys (SMs) naturally control Simian Immunodeficiency Virus (SIV) infection without developing AIDS, unlike humans and rhesus macaques (RMs).
- Previous research suggested attenuated interferon-alpha (IFN-α) responses, linked to Interferon Regulatory Factor-7 (IRF7) variations in SMs, contribute to this non-pathogenic SIV infection.
- Conflicting studies indicate robust IFN-α responses and Interferon Stimulated Genes (ISGs) upregulation in acutely SIV-infected SMs, questioning the 'muted response' hypothesis.
Purpose of the Study:
- To investigate the role of reported IRF7 amino acid substitutions in SMs concerning their non-pathogenic SIV infection.
- To re-evaluate the hypothesis that 'muted' IFN-α responses protect SMs from developing AIDS.
- To compare IFN-α and IRF7 signaling pathways in SMs with those in RMs and humans.
Main Methods:
- Sequencing of all IRF7 exons in 16 SM breeders and variable exons in 177 additional animals.
- Functional assays using recombinant SM IRF7 to assess nuclear translocation and transcriptional activity.
- In vitro stimulation of SM peripheral blood mononuclear cells (PBMCs) with TLR7 agonist CL097 or SIV(mac239) to measure IFN-α/IFN-β mRNA and pDC IFN-α production.
Main Results:
- The previously reported Ser-Gly substitution at position 191 in SM IRF7 was identified as a sequencing error.
- Other reported IRF7 substitutions were found to be minor alleles, and recombinant SM IRF7 showed no functional defects.
- Stimulated SM PBMCs exhibited robust induction of IFN-α and IFN-β mRNA (500-800 fold) and significant IFN-α production by pDCs, comparable to RMs and humans.
Conclusions:
- IFN-α and IRF7 signaling pathways in sooty mangabeys are largely intact and functional.
- The previously proposed 'muted' IFN-α response mechanism is not responsible for AIDS resistance in SIV-infected SMs.
- Minor differences in IFN-α/IRF7 signaling between SMs and RMs are unlikely to explain the distinct disease outcomes of SIV infection.
Related Concept Videos
01:30Inhibitors of Viral Protein Synthesis
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
02:15Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
02:30siRNA - Small Interfering RNAs
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
01:29Immune Response Against Viral Pathogens
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...