Host factors associated with RNA virus pathogenesis: investigating the role of Tetherin in viral replication

Abstract

A virus is a small biological substance, regarded as an obligate intracellular parasite. The virus replicates only within the living cells of plants, animals, and bacteria. In contrast, a virus particle composed of only two macromolecules, nucleic acids (DNA or RNA) as genetic material, and a protein coat that encapsulates this genetic material.[1] [2] Viral infections cause millions of deaths each year and are a primary health concern globally. Many researchers delve into understanding how the virus interacts with its hosts and strategizing appropriate prevention and mitigation measures to address the problems. While many successful antiviral drugs targeting viral proteins are often used, their administration is usually limited to specific viral species or strains. Baltimore classified the virus into seven branches based on their genetic makeup.[2] Compared to DNA viruses, the RNA viruses have low-fidelity polymerase enzymes and therefore prone to rapid mutations, leading to drug-resistant strains. Additionally, viruses encode very few proteins, thus limiting the number of available targets for drug discovery [3]. Hence to discover new antivirals, it's essential to know about host-virus pathogenesis, including how the virus enters the host cells, which proteins are involved in virus entry, replication, translation, assembly, virus antagonizes the host immune responses, etc. In recent years, genome-wide high-throughput RNA interference (RNAi) screening and CRISPR-Cas ribonuclease-based technologies have accelerated the search for such factors involved in virus-host interactions.[4- 7] As a result, we now have detailed knowledge of host factors involved in virus life cycles and their involvement mechanisms. When a virus infects its host, two kinds of host factors get activated. One category associated with viral lifecycle is called essential host factors, and the second types put a restriction on a viral infection called restriction host factors. Both kinds of host factors information are necessary to understand viral pathogenesis. Moreover, this virus and host interactions have resulted in various evolutionary outcomes. During this deep-rooted common history, viruses and hosts have always put stress on each other for survival. Over time, hosts have developed the first defense mechanisms against viruses, called restriction factors. Restriction factors are host proteins that are part of the innate immune system and are potently inhibit pathogen infection.[8] These restriction proteins target the various stages of the viral life cycle. Some factors directly interact with the virus or viral protein, while others indirectly inhibit virus infection by stopping macromolecule synthesis, apoptosis, etc. But with the evolution, viruses have also evolved antagonism mechanisms against these restriction factors. These antagonistic connections between the host factors and the virus proteins induced an evolutionary genetic conflict between the two entities.[9] This genetic contest is also called the "virus host arms race," based on the Red Queen hypothesis, where organisms continuously develop and adapt to survive with changing environments.[10] Moreover, host factors information is essential to understanding viral pathogenesis and discovering new antiviral drugs.