Patent or pathogen associated molecular patterns (PAMPS) interact with receptors on innate immune cells to initiate protective immune responses.
PAMPS for Nucleic Acids: (see Viral Sensing Proteins)
Viral nucleic acids are one of the strongest pathogen-associated molecular patterns (PAMPs), molecules causing particular immune system reactions. PAMPs are recognized by numerous pattern recognition receptors (PRRs) scattered across almost every part of the cell, where they sense the presence of viral particles. Among specific vRNA sensors, retinoic acid-inducible gene I (RIG-I)–like receptors (RLRs), Toll-like receptors (TLRs), 2′-5′-oligoadenylate synthetase (OAS), dsRNA-dependent protein kinase R (PKR), and interferon (IFN)-induced proteins with tetratricopeptide repeats (IFITs) can be found. (Sikorski “Tricks and threats of RNA viruses – towards understanding the fate of viral RNA”, RNA biology, 2021)
During infection, vRNA is introduced into the cell. Foreign nucleic acid present in the cytosol is one of the most potent PAMPs; the host cell recognizes vRNA through the independent activation of several types of innate immune receptors in different cellular compartments.
In the cytoplasm, viral gRNA and its transcriptional intermediates are recognized mostly by RLRs, RIG-I, melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2), which belong to the DExD/H-box helicase family. In endolysosomes, the major RNA sensors that recognize either ds or ss nucleic acid are TLRs 3, 7, and 8. Since newly RNA binding properties of IFITs were discovered, they have been started to be considered as the important ISGs responsible for foreign RNA recognition. (Sikorski “Tricks and threats of RNA viruses – towards understanding the fate of viral RNA”, RNA biology, 2021)
Viral Evasion Mechanisms:
Although human cells have formed various pathways for the detection of viral particles, the multitude of our defence systems have forced viruses to develop sophisticated mechanisms through which to deceive host cells. One of the primary strategies that (+)ssRNA viruses utilize is to ‘hide’ highly recognizable replication intermediates from host sensors e.g. RIG-I and MDA5. Upon entry, coronaviruses and rhinoviruses elaborately modify intracellular membrane organelles, such as endoplasmic reticulum (ER) and mitochondria, to form cytosol isolated organ-like spaces for vRNA replication, also called replication organelles (ROs).
Many RNA viruses have developed additional protection strategies, including protection of vRNA 5′ ends through cap addition or structure imitation. A 5′ cap not only masks viral molecules from detection, but also provides efficient translation of invader proteins. Poliovirus encodes a specialized cap mimicking the VPq protein, attaching it to the 5′ end of vRNAs, thus protecting these nucleic acids from recognition.