RNA sensors as a mechanism of innate immune evasion among SARS-CoV2, HIV and Nipah viruses

Abstract

: Innate immunity is the first line of defence elicited by the host immune system to fight against invading pathogens such as viruses and bacteria. From this elementary immune response, the more complex antigen-specific adaptive responses are recruited to provide a long-lasting memory against the pathogens. Innate immunity gets activated when the host cell utilizes a diverse set of receptors known as pattern recognition receptors (PRR) to recognize the viruses that have penetrated the host and respond with cellular processes like complement system, phagocytosis, cytokine release and inflammation and destruction of NK cells. Viral RNA or DNA or viral intermediate products are recognized by receptors like toll-like receptors(TLRs), nucleotide oligomerization domain(NOD)-like receptors (NLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) thereby, inducing type I interferon response (IFN) and other proinflammatory cytokines in infected cells or other immune cells. But certain viruses can evade the host innate immune response to replicate efficiently, triggering the spread of the viral infection. The present review describes the similarity in the mechanism chosen by viruses from different families -HIV, SARS-CoV2 and Nipah viruses to evade the innate immune response and how efficiently they establish the infection in the host. The review also addresses the stages of developments of various vaccines against these viral diseases and the challenges encountered by the researchers during vaccine development.

A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder

“…Because of such a large genome size, large amounts of RNA particles are released from viruses that are broken down by host immune response. These broken scattered large amount of viral RNA particles are recognized and processed by innate immune system, which leads to Type I interferon (IFN) synthesis, a process that also uses the RA signaling [18] , [19] . The large amount of viral RNA and consequent overwhelming immune stimulation will cause increased RA consumption, and with the time, depletion of retinol reserves in the body [20] , [21] .…”

“…1 ). Viral RNA in the endosomes is mostly recognized byTLR3 and TLR7 while cytosolic viral RNA is recognized by RIG-I like receptor family proteins, such as retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) [18] , [19] , [20] , [23] . RIG-I is the main cytosolic receptor that recognizes cytosolic viral RNA molecules and is responsible for type I interferon synthesis [20] , [24] .Expression of RIG-I is regulated through RA signaling and with the prolonged stimulation, the cellular retinol resources are used up causing depletion of retinol depot in the body [20] , [25] , [26] , [27] .…”

“…Furthermore, monocyte/macrophage associated markers are also upregulated in the blood of COVID-19 patients [222] . In addition, like some viruses, SARS-CoV2 can evade innate immune response mediated through PRR [18] . Upregulation of NKG2A and decreased NK, cytotoxic T, memory CD4, and T regulatory cells are associated with the severity of the COVID-19 disease [127] , [218] , [223] , [224] .…”

“…This recognition of viral RNA leads to synthesis of Type I IFNs through RA signaling [288] , [296] , [297] , [298] , [299] . Type I interferon synthesis is particularly prominent in plasmacytoid dendritic cells in the lungs where ATRA is also highly synthesized [18] , [19] , [196] , [266] , [300] , [301] . Some viruses including SARS-CoV2 have developed mechanisms that evade and antagonize the RIG-I-mediated IFN production pathway [18] , [55] , [302] .…”

Cellular and Molecular Effects of SARS-CoV-2 Linking Lung Infection to the Brain

“…On the other hand, at a later stage, the activation of antiviral programs and the recruitment of non-infected immune cells occur. Virus particles released from the infected dead cells are recognized by endosomal RNA pattern recognition receptors (PRRs) which leads to the activation of the innate immune system and its cellular machinery (39,44). Recent studies reported that not only the main RNA sensors, including cytoplasmic retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5), have a key role in the detection and identification of coronavirus derived PAMPs (45,46), but also pattern recognition toll-like receptors 3 and 7 (TLR-3 and TLR-7) are activated.…”