Viral subversion mechanisms in chronic kidney disease pathogenesis

Abstract

Viruses cannot autonomously replicate but must rely on the host cellular machinery to support their life cycle. Through natural selection, viruses have evolved strategies to co-opt the host organism to be a better site for their propagation. Some of these strategies are directed at the cellular machinery and involve complicated and ingenious solutions to optimize infection, replication, viral gene expression, and new virion assembly and shedding. Other strategies are directed at the host's innate and adaptive immune systems that permit the virus to evade clearance mechanisms. The more common pathogenic viral infections in nephrology-cytomegalovirus, HIV-1, hepatitis C virus, polyomavirus BK, and parvovirus B19-all have acquired subversion strategies that benefit the virus but because they interfere with normal cellular and immune processes also have become pathogenic to the host. In addition, the highly prevalent viruses cytomegalovirus, BK, and B19 cause severe disease only in the setting of immunosuppression, revealing the very delicate balance that some viruses have achieved with their host's immune system. Thus, selective pressure for survival drives both the evolution of more sophisticated viruses and the host immune system as it evolves to combat the environment of adapting and emerging infectious agents. Understanding the molecular mechanisms of these viral subversion strategies may reveal new targets for the development of highly specific antiviral therapies and also aid vaccine development.

Figure 1

Eukaryotic cell barriers to the viral life cycle and types of subversion mechanism employed by the virus. Viruses require the use of the host cellular machinery to replicate their nucleic acid and produce viral proteins for the assembly of new virion. In addition, the virus, whether intracellular and extracellular, must escape the anti-viral defense mechanisms of the host’s immune system. For the virus to survive, it must evolve complex strategies to circumvent any cellular blocks to completing its life cycle and to evade the host immune system.