Arthropod-Borne Disease May Lead to a More Resilient Type I Interferon Response to Coronavirus by Reducing Genetic Defects of Innate Immunity by Natural Selection

This article builds on a previous proposal of a hypothesis where- by repeated arthropod or sand-fly vector infection of humans by novel viruses of zoonotic origins carrying bat or mammalian RNA/ DNA, such as phleboviruses may have resulted in the development of an effective evolutionary immune response to most novel zoonotic viruses such as SARS-CoV-2 through survival of the fittest possi bly over many generations. Phleboviruses and Flaviviruses such as Dengue Fever virus (DENV), can infect many mammalian species, including bats and animal husbandry just like coronaviruses. The resulting mutations when crossing species can expose large populations of humans to novel viruses that find the reactive immunity completely unprepared. Survival over thousands of years of human evolution was likely to be dependent on strong and resilient innate immunity, in the form of the Interferon I system. Phleboviruses and Flaviviruses just like Sars-Covid-1 and 2, have multiple biochemical pathways to suppress the IRF3/7 pathway on different levels, which lead to inefficient production of type 1 interferons and an impaired antiviral response. Recently pub-lished research has shown that 3.5% of patients with life-threatening COVID-19 pneumonia had known AR IRF7 and IFNAR1 deficiencies or AD TLR3, TICAM1, TBK1, and IRF3 deficiencies or new (AD UN - C93B1, IRF7, IFNAR1, and IFNAR2 deficiencies) genetic defects in the TLR3- and IRF7-dependent induction and amplification of type I IFNs. In this paper, it is being proposed that populations of the geographical areas of the respective arthropod-borne disease such as phlebovirus or flavivirus infections may have contributed to select within the populations’ survival of individuals free from genetic defects of these pathways. such Lombardy, Kingdom be necessary to support such a hypothesis.