RNA virus reverse genetics approach for vaccine design and understanding viral pathogenesis

Abstract

From the first discovery of the tobacco mosaic virus (TMV) in plants (1892), followed by the foot and mouth disease virus (FMDV) in animals (1898), and the yellow fever virus (1901) in humans, a plethora of novel viruses have been identified as a leading cause of human infectious diseases[1]. These viral infections impose a significant burden on global health and the global economy and have altered human history affecting the entire ecosystem. Viruses are small biological substances that need a living system (plant, animal, or bacteria) to grow and proliferate. Intriguingly, viruses are composed of the genetic material (nucleic acids as DNA or RNA) and protein components that help maintain genetic information through transmission and replication. Based on genetic makeup, viruses are grouped in two, either DNA or RNA viruses. However, the mechanism of viral reproduction and transmission in DNA viruses differs significantly from that of an RNA virus. Each virus has its niche, host range, and genetic information that it carries. The DNA viruses have a comparatively larger genome than their RNA counterpart. In contrast, the RNA virus genome replication is error-prone due to the low fidelity of the RNA polymerase enzyme. The mutation in the RNA virus helps its evolution and brings better fitness. For example, the current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in multiple mutations leading to increased virus fitness in the context of immune escape and infectivity[2]. Despite the striking decline in mortality aided by vaccination, the threat still looms over us in the form of various strains that are the primary reason for concern. Even slight variations in the genome could bring a significant difference in fatality rates and transmission speed [3, 4]. The reason for this might be the geographical condition and immune response of the individual against the virus.