Question

What portions of our innate defenses does SARS-CoV-2 (or pneumococcal pneumonia) either avoid, overwhelm, or activate. Explain.

Answer 1

SARS CoV is highly pathogenic and the interaction between specific viral genes and the host innate immune system plays a key determinant in the disease outcomes. SARS CoV uses specific strategies to evade and antagonize the sensing and signaling arms of the interferon pathway.

The early innate response to this virus is very important in determining the downstream adaptive immune response. Studies have shown that there are two components of the innate response in which diseases induced by this virus. They are - [a] interactions with macrophages and dendritic cells which shape the early immune response within the lungs and also contribute to virus-induced immune pathology, and [b] the type I IFN system [ which appears to be blocked or evaded by the SARS CoV and other coronaviruses].

IFNs mediate direct antiviral effects that limit viral replication by activating or upregulating several antiviral effectors, like PKR and also by inducing a wide array of IFN inducible genes. SARS CoV, as well as some other viruses, have developed a large variety of avoiding the IFN system. These viral evasion strategies can be categorized as- [a] the virus shields itself from recognition by the host cell sensors that activate the IFN system [avoidance], [b] the virus might actively inhibit the host cell signaling mechanism [supression], and [c] by blocking the type I IFN receptor complex to stop the IFN signaling to prevent an antiviral state within the infected cell.

As for the host cells, they sense the invading CoV through two pathways- [i] Toll-like receptors that detect the viruses and activate the IFN pathway, and [ii] cytoplasmic CARD domain-containing RNA helicases, RIG- I and Mda5, which sense viral RNA in the cytoplasm.