TABLE 1.
Representative immune escape strategies.
| Viruses | Innate elements and mechanisms | References |
| Penetrating physical barrier | ||
| Several viruses, such as Coxsackie, swine vesicular disease virus, adenovirus, reovirus, and others | Breach mucosa by targeting proteins of the apical junctional complex | Gonzalez-Mariscal et al., 2009 |
| ZIKV, DENV, and WNV | Breach skin barrier by infecting permissive cells | Garcia et al., 2017 |
| HIV/SIV | Penetrate physical barrier in multiple ways | Keele and Estes, 2011 |
| Interference with PRRs signaling | ||
| HCV | Extracellular vesicles mask HCV dsRNA to reduce activation of TLR3. | Grünvogel et al., 2018 |
| SARS-CoV | Viral Papain-Like Protease antagonize the TLR7 signaling through removing Lys63-Linked polyubiquitination of TNF receptor-associated factors (TRAF3 and TRAF6) | Li et al., 2016 |
| Marburg virus (MARV) and EBOV | VP35 protein binds to viral dsRNA genomes to inhibit viral sensing by RIG-1 and MDA-5. | Ramanan et al., 2012 |
| HBV | Escape from cGAS sensing by the packaging of the genome into the viral capsid | Verrier et al., 2018 |
| Vaccinia virus (VACV) and IAV | E3L and NS1 proteins of respective viruses sequester viral dsRNA to escape away from sensing by PRRs | Chang et al., 1992; Hatada and Fukuda, 1992 |
| Enterovirus (EV) | Viral proteinases 3Cpro and 2Apro counteracts PRRs signaling by targeting RIG-I and MDA5, respectively. | Feng et al., 2014; Lind et al., 2016 |
| HCV | NS5A protein inhibits TLR signaling by associating with MYD88 | Abe et al., 2007 |
| VACV | A46R targets multiple Toll-like-interleukin-1 receptor adaptors | Stack et al., 2005 |
| Inhibition of transcriptional factors IRF3/7, NF-kB, and AP1 | ||
| SARS-CoV-2 | Suppresses the activation of TRAF3 and TRAF3 and thereby inhibit IRF3/7 and NF-kB activation | Liu et al., 2020 |
| MERS-CoV | Accessory protein ORF8b suppresses MDA5 and TBK1 medicated NF-κB signaling and M protein suppresses type TBK1-dependent phosphorylation of IRF3 | Lui et al., 2016; Lee et al., 2019 |
| IAV | NS1 protein inhibits nuclear translocation of IRFs and NF-kB | Wang et al., 2000 |
| HPV | Interfere in critical ubiquitination events upstream of IRF-3 and NFκB by upregulating the cellular deubiquitinase UCHL1 | Karim et al., 2013 |
| HCV | NS5A viral protein inhibits nuclear translocation of AP-1 by interacting with Grb2 | Macdonald et al., 2003 |
| VACV | Several viral proteins, such as A46, A49, A52, and others inhibit NF-kB activation by multiple mechanisms. | Smith et al., 2013 |
| EV | Viral 3C proteases cleavs IRF7 | Lei et al., 2013 |
| SARS-CoV | Viral M protein inhibits IRF3/7 activation targeting TBK1/IKKε | Siu et al., 2009 |
| EBOV | VP35 protein inhibits IRF3 phosphorylation and subsequent dimerization | Basler et al., 2003 |
| Human papilloma virus 16 | Viral E6 oncoprotein binds to IRF3 and inhibits its transcriptional activity | Ronco et al., 1998 |
| Interference of JAK-STAT signaling | ||
| HPV 18 | Viral E6 oncoprotein binds with Tyk2 and impairs JAK-STAT activation | Li et al., 1999 |
| Mumps virus (MUV) | V protein induces degradation of STAT-1 and STAT-3 | Ulane et al., 2003 |
| HSV-1 | Inhibits JAK-STAT signaling by inducing SOCS3 | Yokota et al., 2004 |
| SeV | C protein inhibits the phosphorylation of STAT1 and STAT2 | Oda et al., 2017 |
| ZIKV, DENV | Induce STAT2 degradation | Morrison et al., 2013; Grant et al., 2016 |
| ZIKV | NS2B3 protein promotes the degradation of Jak1 | Wu et al., 2017 |
| EBOV | EBOV VP24 binds to the α5 and α6 subunits of importin, which are the essential components of the nuclear transporter, to block the nuclear translocation of phosphorylated STAT1 | Shabman et al., 2011 |
| Rotavirus | NSP1 protein inhibits STAT1 activation | Sen et al., 2014 |
| Nipah and Hendra virus | Nucleoproteins inhibit the nuclear accumulation of STAT1 and STAT2 and interfere with their complex formation | Sugai et al., 2017 |
| Parainfluenza virus type 1 | C protein binds and retains STAT1 in perinuclear aggregates at the late endosome | Schomacker et al., 2017 |
| Porcine reproductive and respiratory syndrome virus (PRRSV) | Nsp11 protein interacts with IRF9 and formation and nuclear translocation of the transcription factor complex IFN-stimulated gene factor 3 (ISGF3) | Wang et al., 2019 |
| Antagonizing ISGs | ||
| VACV | Viral E3 protein interacts with human and mouse ISG15 | Eduardo-Correia et al., 2014 |
| MERS-CoV | NS4b proteins cause enzymatic degradation of OAS-RNase L | Thornbrough et al., 2016 |
| HIV-2 | Antagonize tetherin by interacting with viral Rod envelope glycoprotein | Le Tortorec and Neil, 2009 |
| HCV, HIV, IAV, and VACV | E2/NS5A, Tat, NS1, and E3l/K3L viral proteins of respective viruses interact with PKR | Reviewed in Short, 2009 |