Table 3.
TLR3 in human viral pathogenesis
| Virus | Target organ | Disease | Model tested | Role of TLR3 |
|---|---|---|---|---|
| HSV-1 | CNS | Encephalitis, other | Humans with inborn errors of TLR3 | Children with inborn errors in the TLR3 pathway developed HSE; TLR3 is required for protective immunity against HSE by a mechanism that involves production of type I IFN in neurons and oligodendrocytes.59,60 |
| HCV | Liver | Hepatitis, HCC | Hepatoma cells, in vitro | TLR3 mediates pro-inflammatory response.65 |
| Kidney | Glomerulonephritis | Mesangial cells, in vitro | Up-regulation of TLR3 mRNA expression in HCV-positive glomerulonephritis that correlated with enhanced RANTES and MCP-1. | |
| Immune complexes containing viral RNA may activate mesangial TLR3 during HCV infection, thereby contributing to chemokine/cyokine release, effecting proliferation and apoptosis.66 | ||||
| HBV | Liver | Hepatitis, hepatocellular carcinoma | Humans | TLR3 polymorphisms are associated with acute-on-chronic liver failure, and hepatocellular carcinoma.67,68 |
| Influenza, A/H1N1/2009 | Lung | Pneumonia | Humans | A TLR3 polymorphism correlates with increased risk of pneumonia in children.69 |
| Influenza A | CNS, brain | Encephalopathy | Humans | A missense mutation (F3035) in the TLR3 gene correlated with encephalopathy in IAV-infected patients.63 |
| TBEV | CNS | Encephalitis | Humans | The wild-type rs3775291 TLR3 allele was more common among TBE patients than among healthy controls, suggesting that TLR3 may be a risk factor for TBEV infection.64 |
| Rotavirus | Intestine | Gastrointestinal | Humans | Up-regulation of epithelial TLR3 expression during infancy might contribute to the age-dependent susceptibility to rotavirus infection.39 |
| HIV-1 | CD4+ T cells, macrophages, others | Immunodeficiency, encephalitis, other | In vitro and in vivo | Activation of the TLR3 pathway enhances the induction of HIV-specific CD8+ cytotoxic T lymphocytes.72 |
| Activation of the TLR3 pathway with poly(I:C) induces an antiviral state that limits HIV-1 infection in primary human macrophages70 and human fetal astrocytes.71 | ||||
| Potential detrimental contribution of TLR3 in HIV-1-induced myopathies.74 |
A list of definitions for the abbreviations appearing in this Table can be found at the beginning of the article.