Viral counterattack against the host innate immune system

Abstract

npg Paramyxoviruses evade antiviral immune response using a small nonstructural protein, V, which binds to the host dsRNA sensor MDA5 and prevents it from activating the interferon signaling pathway. A recent crystal structure of the V protein in complex with MDA5, published in Science, revealed that V disrupts the structure of MDA5 and is integrated into the MDA5 protein fold, providing an intriguing new example of viral mimicry as a countermeasure against the host immune system.Effective immune response against viruses requires efficient recognition of viral RNAs by host innate immune receptors. To defend against such recognition, viruses encode proteins that either sequester viral RNAs from the host immune system, or directly bind and inhibit (or cleave) immune receptors or other molecules involved in the antiviral signaling pathways. Such viral proteins include VP35 from Ebola virus and NS1 from influenza A virus, which bind to viral double-stranded RNA (dsRNA); K3L from vaccinia virus, which binds to a viral RNA receptors, PKR, and NS3-4A from hepatitis C virus, which cleaves MAVS, a common signaling adaptor for viral RNA receptors, RIG-I and MDA5. Paramyxoviruses encode a nonstructural protein, V, that binds to MDA5 and prevents viral RNA recognition and interferon signal activation. Understanding the complex arms race between the host and viruses would thus require detailed knowledge of both the receptor:viral RNA and receptor:viral

Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic

“…The paternal effects of dietary factors or psychological stress on F1 offspring metabolism have been reported. [ 9–12 ] However, the transgenerational effects across multiple generations remain unclear. Exposures of gestating females to endocrine‐disrupting compounds have been shown to affect adiposity in offspring of multiple generations, although it is unclear whether it is transmitted through the male germline, female germline, a combination of both germlines, or other mechanisms.…”

“…[ 7 ] By comparison, exposure to adult males followed by exclusive male‐lineage breeding has fewer confounding effects, which provides an efficient way to distinguish transgenerational effects from intergenerational effects. [ 8 ] Although the paternal effects of dietary factors or psychological stress have been studied on F1 offspring, [ 9–12 ] it remains underexplored how paternal exposure to environmental chemicals affects metabolic health in F1 offspring. More importantly, the transgenerational effects of paternal exposures across multiple generations were unclear in mammals.…”