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cGAS–STING-mediated sensing pathways in DNA and RNA virus infections: crosstalk with other sensing pathways

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Abstract

Viruses cause a variety of diseases in humans and other organisms. The most important defense mechanism against viral infections is initiated when the viral genome is sensed by host proteins, and this results in interferon production and pro-inflammatory cytokine responses. The sensing of the viral genome or its replication intermediates within host cells is mediated by cytosolic proteins. For example, cGAS and IFI16 recognize non-self DNA, and RIG-I and MDA5 recognize non-self RNA. Once these sensors are activated, they trigger a cascade of reactions activating downstream molecules, which eventually results in the transcriptional activation of type I and III interferons, which play a critical role in suppressing viral propagation, either by directly limiting their replication or by inducing host cells to inhibit viral protein synthesis. The immune response against viruses relies solely upon sensing of viral genomes and their downstream signaling molecules. Although DNA and RNA viruses are sensed by distinct classes of receptor proteins, there is a possibility of overlap between the viral DNA and viral RNA sensing mechanisms. In this review, we focus on various host sensing molecules and discuss the associated signaling pathways that are activated in response to different viral infections. We further highlight the possibility of crosstalk between the cGAS-STING and the RIG-I-MAVS pathways to limit viral infections. This comprehensive review delineates the mechanisms by which different viruses evade host cellular responses to sustain within the host cells.

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Acknowledgements

We acknowledge the support of Ramalingaswami Fellowship Grant (BT/RLF/Re-entry/09/2015), Government of India, Ministry of Science and Technology, Department of Biotechnology (DBT) and Early Career Research Award Grant (File No. ECR/2018/002114) from the Science and Engineering Research Board (SERB), Department of Science and Technology, Government of India, to author Jawed Iqbal. We also acknowledge the support of a non-NET fellowship from the Union Grant Commission (UGC) to Saleem Anwar and Khursheed Ul Islam, and a Senior Research Fellowship from ICMR, Government of India, to Md Iqbal Azmi.

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  1. Multidisciplinary Centre for Advanced Research and Studies, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India

    Saleem Anwar, Khursheed Ul Islam, Md Iqbal Azmi & Jawed Iqbal

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  1. Saleem Anwar
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  2. Khursheed Ul Islam
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  3. Md Iqbal Azmi
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  4. Jawed Iqbal
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Correspondence to Jawed Iqbal.

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Anwar, S., Ul Islam, K., Azmi, M.I. et al. cGAS–STING-mediated sensing pathways in DNA and RNA virus infections: crosstalk with other sensing pathways. Arch Virol 166, 3255–3268 (2021). https://doi.org/10.1007/s00705-021-05211-x

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  • DOI: https://doi.org/10.1007/s00705-021-05211-x

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