High throughput proteomic analysis and a comparative review identify the nuclear chaperone, Nucleophosmin among the common set of proteins modulated in Chikungunya virus infection

Abstract

Chikungunya remained as a neglected tropical disease till its re-emergence in 2005 in the La RéUnion islands and subsequently, in India and many parts of South East Asia. These and the epidemics that followed in subsequent years ran an explosive course leading to extreme morbidity and attributed mortality to this originally benign virus infection. Apart from classical symptoms of acute fever and debilitating polyarthralgia lasting for several weeks, a number of complications were documented. These included aphthous-like ulcers and vesiculo-bullous eruptions on the skin, hepatic involvement, central nervous system complications such as encephalopathy and encephalitis, and transplacental transmission. The disease has recently spread to the Americas with its initial documentation in the Caribbean islands. The Asian genotype of this positive-stranded RNA virus of the Alphavirus genus has been attributed in these outbreaks. However, the disease ran a similar course as the one caused by the East, Central and South African (ECSA) genotype in the other parts of the world. Studies have documented a number of mutations in the re-emerging strains of the virus that enhances mosquito adaptability and modulates virus infectivity. This might support the occurrence of fiery outbreaks in the absence of herd immunity in affected population. Several research groups work to understand the pathogenesis of chikungunya and the mechanisms of complications using cellular and animal models. A few proteomics approaches have been employed earlier to understand the protein level changes in the infected cells. Our present study, which couples a high throughput proteomic analysis and a comparative review of these earlier studies, identifies a few critical molecules as hypothetical candidates that might be important in this infection and for future study.

Addressing knowledge gaps in molecular, sero-surveillance and monitoring approaches on Zika epidemics and other arbovirus co-infections: A structured review

“…From the collaborated evidence it is clear that ZIKV-RT-PCR has the desired specificity and sensitivity for detection on applicable flavivirus based on clinical symptoms observed ( Robin and Mouchet, 1974 , Hegde et al, 2015 , Weaver and Forrester, 2015 , Faye et al, 2013 , Lanciotti et al, 2008 ). In its enhancement and scaling up as a screening technique, complementing more funding and investment in novel, safe and efficacious therapeutics agents and vaccines in meeting the vulnerable population and travel medicine immunization programs hopes and needs will be of immense benefit to cases profiling and management ( Chang et al, 2015 , Abraham et al, 2015 , Petersen et al, 2016b ).…”

Chikungunya and diabetes, what do we know?

“…Diabetic patients are more susceptible to infection, and this can impact on glucose metabolism [ 21 ]. Probably, this stress aggravates insulin resistance in these cases which justify the metabolic impact of CHIKV [ 22 ]. In addition, DM is not just a disorder of glucose metabolism, but a chronic inflammatory condition characterized by multiple changes in lipid profiles and blood glucose [ 23 ].…”

“…Another important issue is how this inflammatory and immune response occurs in diabetic patients, as well as whether the virus itself interferes with insulin secretion or the glycemic control. Following this line of reasoning, one study, by analyzing the metabolism of various proteins after inoculation of the CHIKV, found that some of the altered proteins were involved in lipid metabolism and glucose [ 22 ]. Such data suggest that the virus modifies the action of these proteins in the body, resulting in a negative impact of metabolic control.…”

Chikungunya Virus Infection and Diabetes Mellitus: A Double Negative Impact

“…In addition to insulin resistance related to most of infectious intercurrent illnesses, CHIKV infection appears to have an additional effect on glycemic levels in DPs, as judged by the magnitude of the hyperglycemic effect. A recent proteomics analysis of CHIKV infection in vitro demonstrated that among 45 downregulated proteins in cells infected with CHIKV, proteins involved in carbohydrate and lipid metabolism predominated,18 possibly indicating that CHIKV may have an inherent effect on glucose metabolism that particularly affects DPs. Obviously, more investigations are needed to find out the explanations of the deleterious correlation between diabetes and CHIKV infection.…”