Mass spectrometric analyses of proteomic dysregulation by Zika Virus in astrocytic cells
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Date
2022-07-26
Authors
Sher, Affan Ali
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Abstract
Zika virus (ZIKV), an arbovirus, is primarily transmitted via the Aeges aegyptii mosquito species. The first major outbreak of ZIKV was reported in 2013 and 2014 in Micronesia and it wasn’t until summer and fall of 2016 that evidence of its cases and transmission was reported in the US. In 2016, WHO declared it a Public Health Emergency of International Concern. Owing to majority of its cases being asymptomatic or mildly symptomatic, the reporting of ZIKV transmission and infection has been relatively limited. The most common symptoms of ZIKV infection include acute fever, arthralgia, conjunctivitis, maculopapular rash, muscle/joint pain, headache and malaise. Over time, its mode of transmission has also been associated with perinatal, in utero, sexual and transfusion transmission. Among the pathological conditions associated with ZIKV, the most common ones for Central Nervous System include (meningo)encephalitis, myelitis and acute disseminated encephalomyelitis (ADEM) and the most common ones for Peripheral Nervous System include Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy and acute transient polyneuritis. Therefore owing to lack of effective diagnoses, vaccination and treatment availability, the need for understanding ZIKV infections in the nervous system is warranted. Since astrocytes are a major cell type in the CNS and are known to support ZIKV infection, this study performs mass spectrometry to analyse the alterations in the expression profile of the ZIKV infected human glioblastoma cells (U251 cells) as model cell line for astrocytic cells. Ingenuity Pathway Analyses, following two tailed students t-test and z-score analyses, show cellular networks, functions and pathways pertaining to antimicrobial response, cell death/survival, energy production, antigen presentation, neuromuscular disease, interferon signaling and Th1 pathway to be significantly dysregulated by ZIKV at 48hrs post infection. The last part of this study focuses on siRNA mediated knockdown for 50 proteins (mentioned in Table 2). 4, namely HLA-A, HSPA5, IGFBP5 and PSMA2, are chosen from there and they show an increase in ZIKV titres 48hrs post infection. In addition, ZIKV is also shown to restore HLA-A expression in HLA-A siRNA KD cells by 48hrs post infection highlighting the role ZIKV potentially plays in bypassing the siRNA mediated KD in order to aid its replication and synthesis inside the U251 cells.
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Keywords
Zika, Mass Spectrometry, Proteomics, Astrocytes, siRNA knockdown, U251 cells