Toll-Like Receptors Recognizing Viral Double-Stranded RNA

In order to protect against infection, one of the things the body must initially do is detect the presence of microorganisms. The body does this by recognizing molecules unique to microorganisms that are not associated with human cells. These unique molecules are called pathogen-associated molecular patterns or PAMPS and they bind to pattern recognition receptors called toll-like receptors (TLRs) found on host defense cells. For example, most viral genomes contain a high frequency of unmethylated cytosine-guanine dinucleotide sequences (a cytosine lacking a methyl or CH3 group and located adjacent to a guanine). Mammalian DNA has a low frequency of cytosine-guanine dinucleotides and most are methylated. In addition, most viruses produce unique double-stranded viral RNA, and some viruses produce uracil-rich single-stranded viral RNA during portions of their life cycle. The binding of these unique viral molecules bind to the endodsomal TLRs of defense cells such as macrophages and dendritic cells triggers the production of antiviral cytokines called type I interferons that are able to block viral replication.

a. TLR-3 - binds double-stranded viral RNA;
b. TLR-7 - binds single-stranded viral RNA, such as in HIV, rich in guanine/uracil nucleotide pairs;
c. TLR-8 - binds single-stranded viral RNA;
d. TLR-9 - binds unmethylated cytosine-guanine dinucleotide sequences (CpG DNA) found in bacterial and viral genomes but uncommom or masked in human DNA and RNA.

Interferons induce uninfected cells to produce enzymes capable of degrading mRNA. These enzymes remain inactive until the uninfected cell becomes infected with a virus. At this point, the enzymes are activated and begin to degrade both viral and cellular mRNA. This not only blocks viral protein synthesis, it also eventually kills the infected cell.

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Updated: Oct., 2008
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