Metabolic reprogramming and immune regulation in viral diseases

Abstract

The recent outbreak and transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide and the ensuing coronavirus disease 2019 (COVID-19) pandemic has left us scrambling for ways to contain the disease and develop vaccines that are safe and effective. Equally important, understanding the impact of the virus on the host system in convalescent patients, healthy otherwise or with co-morbidities, is expected to aid in developing effective strategies in the management of patients afflicted with the disease. Viruses possess the uncanny ability to redirect host metabolism to serve their needs and also limit host immune response to ensure their survival. An ever-increasingly powerful approach uses metabolomics to uncover diverse molecular signatures that influence a wide array of host signalling networks in different viral infections. This would also help integrate experimental findings from individual studies to yield robust evidence. In addition, unravelling the molecular mechanisms harnessed by both viruses and tumours in their host metabolism will help broaden the repertoire of therapeutic tools available to combat viral disease.

The Lactate and the Lactate Dehydrogenase in Inflammatory Diseases and Major Risk Factors in COVID-19 Patients

“…The molecular basis of COVID-19’s dysregulated glucose metabolism is poorly understood. The discovery of the molecular processes used by viruses and cancers in their host metabolism expands the therapeutic toolbox available to fight viral disease [ 38 , 39 ]. Although viral infection is known to alter host cell metabolism for more than half a century, the processes and effects of virus-induced metabolic reprogramming have been examined in depth only recently.…”

Coronavirus disease 2019 (COVID‐19) update: From metabolic reprogramming to immunometabolism

“…46 Some viral proteins employ host metabolic activities to induce dysregulation in various cellular pathways, increasing cancer risk. 43 For example, the human papillomavirus 16 E6 protein inhibited hypoxia-inducing factor-alpha (HIF-α) degradation and thereby enhanced glycolysis in cells infected with this virus. 47 In Vero cells, it has been found that Enterovirus EV71 can increase glutamine metabolism, whereas pharmaceutical suppression of pyrimidine metabolism enzymes reduced viral proliferation.…”

“…61,67 Iron is thought to be involved in the cellular metabolism of all living organisms, such as viruses and their mammalian hosts. 43 A differing class of mediators tightly regulates the host's concentration of iron is circulating, including both unbound and heme-bound forms, in a way that mitigates oxidative injury (iron-mediated) and postpones the migration and development of pathogenic organisms both extracellularly (as in blood that harbor's specific parasites and bacteria) and inside cells (as fundamentally observed with viruses). 43 Although most intrinsic iron is recycled through the formation and destruction of erythrocytes, cells also have complicated systems for iron storage.…”

“…Viruses are one of the biological entities that significantly restructure the host cell's metabolic process to survive their life cycle, naming them “metabolic engineers.” 42 Similarities and variations exist in various viruses regarding host cell invasion, proliferation, and spread 43 . Viruses may also attack the host's immune system, potentially directly or indirectly.…”

SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE

“…Metabolic Reprogramming is a phenomenon observed in cancer, viral infection, and neurodegenerative diseases [ 5 , 6 , 7 , 8 , 9 ], which results in the rewiring of the cellular metabolism to support the increasing energy demand. Cancer cells and viruses use this mechanism to synthesize free nucleotides and amino acids necessary for their assembly and replication [ 10 , 11 ].…”