Double-edged sword of JAK/STAT signaling pathway in viral infections: novel insights into virotherapy

Mahjoor, Mohamad; Mahmoudvand, Golnaz; Farokhi, Simin; Shadab, Alireza; Kashfi, Mojtaba; Afkhami, Hamed

doi:10.1186/s12964-023-01240-y

Cell Communication and Signaling

Table 3 Overview of the strategies implemented by viruses to evade the JAK/STAT cascade

From: Double-edged sword of JAK/STAT signaling pathway in viral infections: novel insights into virotherapy

Mechanism	Virus applying the mechanism	JAK/STAT component affected	Evasion mediator	Outcome
Suppression of IFN signaling	West Nile virus	STAT1	NS5	Antagonizing type I IFN-mediated JAK-STAT signaling [32]
	Kaposi's sarcoma-associated herpesvirus	JAK1, TyK2, and STAT2	RIF	Blockage of IFN signaling by producing inhibitory complexes containing IFNAR subunits [33]
	Herpes Simplex Virus 1	JAK1	UL36USP	Suppression of IFN-β-induced activation of ISRE promoter and transcription of ISGs [34]
Promotion of proteasomal degradation through ubiquitination	Hepatitis C virus	STAT3	Direct ubiquitination of STAT3	Inhibition of IFN-α responses [35]
	HIV	STAT1 and STAT3	Vif	Blockage of IFN-α functions [36]
	Porcine reproductive and respiratory syndrome virus	STAT2	Nsp11	Inhibition of IFN antiviral activity [37]
Inhibition of STAT phosphorylation	Japanese encephalitis virus	STAT1 and Tyk2	Protein tyrosine phosphatases	Suppression of the induction of IFN-stimulated genes and the antiviral function of IFN-α [38]
	Human papilloma virus	STAT1, STAT2, and Tyk2	Direct physical interaction with the receptor-associated kinases	Blocking the antiviral function of IFNs [39]
	Sendai virus	Tyk2, STAT1, STAT2, and STAT3	C proteins	Inhibition of the antiviral function of IFN- α [40]
	Varicella zoster virus	STAT2	ORF63	Resistance to IFN treatment [41]
Blockage of the nuclear transport of ISGF3	PRRSV	STAT1 and STAT2	Nsp1β	Suppression of the IFN-mediated antiviral responses [42]
	Porcine epidemic diarrhea virus nsp7	STAT1 and STAT2	Interaction with the DNA binding domain of STAT1/STAT2	Suppression of type I IFN signaling pathway [43]
	Herpes simplex virus type 2	STAT1 and STAT2	ICP22	Interference with IFN type 1 signaling [44]
Upregulation of SOCS	Influenza A virus	JAK1	Upregulating mRNA level of SOCS1	Antagonizing type I and type II IFN responses [45]
Upregulation of SOCS	Enterovirus 71	STAT3	Upregulating mRNA level of SOCS1 and SOCS3	Downregulation of the JAK/STAT signaling pathway in an interferon-independent way [46]

IFN Interferon, HIV Human immunodeficiency virus, PRRSV Porcine reproductive and respiratory syndrome virus, SOCS Suppressor of cytokine signaling, ISRE Interferon-sensitive response element, ISGs Interferon-stimulated genes

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ISSN: 1478-811X

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