This pathway describes the activation of the human MAPK signaling system during human coronavirus infection, per Fung and Liu, Figure 7 [10.1146/annurev-micro-020518-115759]. The MAPK signaling system regulates response to different environmental stimuli, e.g. inflammation due to infection. Its downstream effects include regulation of cell cycle, apoptosis, differentiation and immune response. During coronavirus infection, three MAPK signaling pathways were studied and described. The p38 pathway (MAPK11 - MAPK14) leads to stimulation of apoptosis via CHOP (DDIT3) while the ERK pathway (MAPK1 and MAPK3) counteracts apoptosis stimulation and supports cell survival by stimulating ATF2 and FOS. The JNK pathway (MAPK 8 - MAPK10) inhibits cell survival protein BCL2, thus stimulating apoptosis but also stimulating the AP1 complex that leads to the production of effectors to fight the infection. The interplay of apoptosis stimulation and cell survival is not yet fully understood in SARS-CoV-2 infection. a72 MEKK1 MLK1 MLK2 MLK3 JNK AP1 AP1 p38 p38 CHOP p38 MEKK4 ERK1 MKK7 ERK2 JNK b6f MKK4 MKK3 p38 MKK1 RSK c-FOS JNK RSK MKK6 MKK2 RSK b6f b6f b6f b6f b6f signaling pathway PW:0000003 Pathway Ontology viral infectious disease DOID:934 Human Disease Ontology severe acute respiratory syndrome DOID:2945 Human Disease Ontology p38 MAPK signaling pathway PW:0000198 Pathway Ontology COVID-19 DOID:0080600 Human Disease Ontology 31226023 PubMed Human Coronavirus: Host-Pathogen Interaction. Annu Rev Microbiol 2019 Fung TS Liu DX 10.1101/2020.03.15.20033472 DOI Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19 https://doi.org/10.1101/2020.03.15.20033472 2020 Lulin Huang Yi Shi Bo Gong Li Jiang Xiaoqi Liu Jialiang Yang Juan Tang Chunfang You Qi Jiang Bo Long Tao Zeng Mei Luo Fanwei Zeng Fanxin Zeng Shuqiang Wang Xingxiang Yang Zhenglin Yang