Table 2. Selection of antiviral factors indirectly targeting viral replication (abbreviations are explained in the text).
| Antiviral factor(s) | Target(s) | Discrimination between self and non-self | Effect on viral replication | (Potential) Unwanted effects on host cell | |
|---|---|---|---|---|---|
| Immediate | Long term | ||||
| IFITM3 | VAPA, OSBP | Membrane curvature, lipid composition | Impaired fusion of viral and host membranes | Impaired fusion of cellular membranes | Constraints in membrane fusion (e.g. syncytin-mediated trophoblast fusion) |
| CH25H | Cholesterol | Not known | Impaired fusion of viral and host membranes, impaired membraneous web formation | Impaired fusion of host membranes (?) | |
| SAMHD1 | dNTPs | Not known | Limits reverse transcription/viral DNA replication | Inhibition of host DNA replication | Regulation of SAMHD1 activity in dividing cells |
| MxB | Nucleoporins | Simultaneous interaction with viral (capsid) proteins | Reduced nuclear import of subviral complexes | Impaired nuclear pore transport | Evolution of diverse nuclear pore variants |
| KAP1 | NuRD complex/HDACs, SETDB1, transcription factors | Not known | Suppression of viral gene transcription, latency | Suppression of host gene transcription | |
| TRIM22 | Sp1 | Not known | Reduced Sp1-driven expression of viral genes | Reduced Sp1-driven expression of host genes | Constraints in Sp1-driven gene expression |
| IFI16, MNDA, IFIX | Sp1 | Chromatinization status of the DNA | Reduced Sp1-driven expression of viral genes | Reduced Sp1-driven expression of host genes | Constraints in Sp1-driven gene expression |
| PKR | eIF-2α | Activation by dsRNA | Reduced translation of viral mRNA | Reduced translation of host mRNA | Avoidance of dsRNA |
| IFITs | eIF3 | IRES, modification of 5′ RNA ends | Inhibition of translation | Inhibition of translation (?) | Depletion of IRES structures, mRNA capping (methylated) |
| SLFN11 | tRNA | preferred targeting of tRNAs exploited by viruses | Reduced translation of viral mRNA | Reduced translation of cellular mRNA | Specific codon usage pattern |
| PAR1, GBP2, GBP5 | Furin | Not known | Impaired furin-mediated maturation of viral (glyco)proteins | Impaired proteolytic activation of host proteins | Constraints in furin-mediated protein cleavage |
| HERC5/ISG15 | Numerous host proteins (e.g. IRF3, RIG-I, PKR) | Preferred ISGylation of newly translated proteins | Several proposed inhibitory mechanisms | Modulation of host protein stability and function | |
| Viperin | FPPS, CTP |
Not known | Inhibition of viral budding, inhibition of viral RNA polymerization | Inhibition of cellular protein secretion and potentially cellular RNA synthesis | |