Viral diseases and their implications on host metabolism


The threat of emerging and re-emerging viral diseases continues to be a major cause of public health problems. SARS-CoV-2, the novel coronavirus that was first found in Wuhan, Hubei Province, China in December 2019, has emerged as one of the most devastating pandemics in history. Furthermore, it affected global economies and resulted in widespread unemployability. Hence, it has become all the more important to understand viruses, their interactions with the host system, transmission, and prevention methods like immunization.


Viruses are responsible for several infectious diseases like influenza, AIDS, polio, Ebola, measles, and a few types of cancer. All viruses being obligatory intracellular parasites cannot reproduce unless are associated with a host cell. They take over the host cell's internal machinery to synthesize its raw materials and replicate itself. A virus contains a small segment of genetic material, RNA or DNA, surrounded by a protein coat called the capsid. This surface may contain one or multiple copies of cell surface proteins which helps them to attach to host cells and allow them to enter inside and cause infectious diseases.


Viruses rely on host metabolism to obtain the energy and materials they require to replicate, such as nucleotides, amino acids, or lipids. Through direct targeting of metabolic enzymes, signaling pathways, or other organelles with crucial metabolic functions, viruses may reprogram metabolism.

Advanced technologies for analyzing cell metabolic alterations have shown that viruses enhance specific anabolic pathways and are essential for host-pathogen interactions.

This is mainly done by increasing the uptake of extracellular carbon sources (like glucose and glutamine) which causes the glycolytic flux to increase and get redirected more towards the production of lactate from pyruvate. Most viruses also increase the flux through Pentose Phosphate Pathway (PPP) which is indispensable for ribonucleotides synthesis to generate viral genetic material. Their replication also relies on host cell Fatty Acid (FA) synthesis machinery for viral genome replication and virion production. Hence, lipogenesis plays a pivotal role in lipid formation which the virus needs for the production of the viral envelope and surface protein. Hence, by modifying the utilization of carbon resources, the virus-infected cell can become a niche for the production of new virus particles.


The consequences of these viral infections can differ in hosts with underlying diseases like diabetes, cardiovascular, endocrine diseases, and obesity. The coronavirus disease in 2019 (COVID-19) has made this an important issue as diabetics have been documented to show severe cases of infection. This relationship between the severity of COVID-19 and the uncontrolled blood glucose levels in diabetics, further proves that various facets of metabolism are disturbed during viral infections. The heterogeneous outcomes due to these comorbid conditions imply that adjusting the metabolic environment in the host could be one way to control virus-host relationships.


It is imperative to analyze how viruses alter cellular metabolism and how their interaction with different signaling pathways of the host works. Understanding major bottlenecks in this area can prove to be a novel approach to controlling the outcomes of viral infections and developing specific antiviral therapies. For example, Defense Research and Development Organization (DRDO) introduced an anti-COVID-19 drug called 2DG (2-Deoxy-D-glucose) which targets and downregulates PPP and ultimately hinders viral replication. Another anti-viral drug for COVID is Remdesivir, which inhibits the process of nucleotide production which renders the virus unable to synthesize genetic material for itself. Hence, future research is needed to identify whether the therapeutic strategies are clinically applicable and if they have the potential to provide personalized treatment.

 

This work was created as part of a science communication internship at BioXspace.

Edited and approved by Dr. Jyoti Chhibber-Goel and Dr. Bharti Singal

#virus #metabolism #COVID19 #antiviral #viralinfection #treatment

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