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Virology
Chapter 33 notes: Intrinsic cellular defense against virus infection

1. Toll- like receptors sense virus infections a. Toll-like receptors (TRL) i. Located on the cell surface or in endosomal membranes = recognize conserved structures found in pathogens ii. Highly conserved receptors from flies humans iii. Most mammals have between 10-15 (humans = 10) iv. TLR – 2: lipoproteins/glycoproteins (mealsels, hepB, herpes) v. TLR– 3: dsRNA (west nile, influenza) vi. TLR – 5: flagellin vii. TLR – 7/8: ssRNA: (HIV, influenza..) 1. Recognize the guanine and uridine rich single stranded RNAs) viii. TLR 9: unmethlylated CpG DNA (vaccinia, hepB, herpes) 2. Both single and dsDNA b. Many DNA viruses transcribe both strands of certain regions of their DNA genomes = self- complementary RNAs (dsRNA) c. ssRNA viruses = replicate their genome by synthesizing full length complementary RNA stands that can form dsRNA by hybridizing to the template RNA strand ix. ***The presence of dsRNA is the MOST RELIABLE indicator that a replicating virus is present*** x. TLR 3- recognizes dsRNA xi. Expression of TLR3 is found on many cells – dendritic cells, macrophages, fibroblasts, epithelial cells xii. ****only binds to dsRNA at a low pH indicating that it happens in endosomes 2. Detection of viral RNAs: d. RIG-I (RNA helicase, retinoic acid inducible gene I) xiii. short dsRNA, ssRNA with a 5’ triphosphate group e. MDA 5 (melanoma differentiation association gene 5) xiv. Long dsRNA f. *both recognize RNAs from different viruses g. *unlike the TLR they are soluble and cytosolic proteins that can bind to ncleic acids localized in the cytosol 3. Recognition of dsDNA in the cytoplasm (three different cellular components) h. *sign of infection because dsDNA is not

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