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Updated: Jun 1, 2026
Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
Human metapneumovirus glycoprotein G inhibits TLR4-dependent signaling in monocyte-derived dendritic cells
Deepthi Kolli1, Xiaoyong Bao, Tianshuang Liu
1Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
Abstract:
Human metapneumovirus (hMPV) is a major cause of upper and lower respiratory infections in children and adults. Recent work from our group demonstrated that hMPV G glycoprotein is an important virulence factor, responsible for inhibiting innate immune responses in airway epithelial cells. Myeloid dendritic cells (DCs) are potent APCs and play a major role in initiating and modulating the innate and adaptive immune responses. In this study, we found that TLR4 plays a major role in hMPV-induced activation of monocyte-derived DCs (moDCs), as downregulation of its expression by small interfering RNA significantly blocked hMPV-induced chemokine and type I IFN expression. Similar results were found in bone marrow-derived DCs from TLR4-deficient mice. moDCs infected with a virus lacking G protein expression produced higher levels of cytokines and chemokines compared with cells infected with wild-type virus, suggesting that G protein plays an inhibitory role in viral-induced cellular responses. Specifically, G protein affects TLR4-dependent signaling, as infection of moDCs with recombinant hMPV lacking G protein inhibited LPS-induced production of cytokine and chemokines significantly less than did wild-type virus, and treatment of moDCs with purified G protein resulted in a similar inhibition of LPS-dependent signaling. Our results demonstrate that hMPV G protein plays an important role in inhibiting host innate immune responses, likely affecting adaptive responses too.
Insights
Human metapneumovirus (hMPV) G glycoprotein inhibits innate immunity by blocking TLR4 signaling in dendritic cells. This viral protein suppresses immune cell responses, impacting the host
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human metapneumovirus (hMPV) causes significant respiratory infections.
- The hMPV G glycoprotein is identified as a key virulence factor.
- Myeloid dendritic cells (DCs) are crucial for initiating and regulating immune responses.
Purpose of the Study:
- To investigate the role of TLR4 in hMPV-induced DC activation.
- To elucidate the function of hMPV G glycoprotein in modulating innate immune responses.
- To determine how hMPV G protein influences TLR4-dependent signaling pathways.
Main Methods:
- Small interfering RNA (siRNA) was used to downregulate TLR4 expression in monocyte-derived DCs (moDCs).
- Bone marrow-derived DCs from TLR4-deficient mice were utilized.
- Experiments involved infection with wild-type hMPV, G protein-deficient hMPV, and stimulation with LPS.
- Purified hMPV G protein was used to assess its direct effects on signaling.
Main Results:
- TLR4 is essential for hMPV-induced activation of moDCs, evidenced by blocked chemokine and type I IFN expression upon TLR4 downregulation.
- DCs infected with G protein-deficient hMPV exhibited enhanced cytokine and chemokine production compared to those infected with wild-type virus.
- hMPV G protein was shown to inhibit TLR4-dependent signaling, as evidenced by reduced cytokine/chemokine production after LPS stimulation in the presence of G protein.
Conclusions:
- hMPV G glycoprotein significantly inhibits host innate immune responses.
- The G protein's inhibitory mechanism involves interference with TLR4-dependent signaling pathways.
- These findings suggest hMPV G protein's role in immune evasion and potential impact on adaptive immunity.
