Postgenomics Biomarkers for Rabies—The Next Decade of Proteomics

Abstract

Rabies is one of the oldest diseases known to mankind. The pathogenic mechanisms by which rabies virus infection leads to development of neurological disease and death are still poorly understood. Analysis of rabies-infected proteomes may help identify novel biomarkers for antemortem diagnosis of the disease and target molecules for therapeutic intervention. This article offers a literature synthesis and critique of the differentially expressed proteins that have been previously reported from various in vitro/in vivo model systems and naturally infected clinical specimens. The emerging data collectively indicate that, in addition to the obvious alterations in proteins involved in synapse and neurotransmission, a majority of cytoskeletal proteins are relevant as well, providing evidence of neuronal degeneration. An interesting observation is that certain molecules, such as KPNA4, could be potential diagnostic markers for rabies. Importantly, proteomic studies with body fluids such as cerebrospinal fluid provide newer insights into antemortem diagnosis. In order to develop a complete integrative biology picture, it is essential to analyze the entire CNS (region-wise) and in particular, the brain. We suggest the use of laboratory animal models over cell culture systems using a combinatorial proteomics approach, as the former is a closer match to the actual host response. While most studies have focused on the terminal stages of the disease in mice, a time-series analysis could provide deeper insights for therapy. Postgenomics technologies such as proteomics warrant more extensive applications in rabies and similar diseases impacting public health around the world.

Proteomics Study on the Cerebrospinal Fluid of Patients with Encephalitis

“… 13 Besides, a review on the proteomic analysis of CSF from rabies infection also illustrated that it is related to synaptic and neurotransmission. 14 Inhibiting neuroinflammation is an important strategy in the treatment of brain disease. Xia et al demonstrated the important role of the dopamine receptor as an important G-protein-coupled receptor in inflammation-associated glial cells.…”

Applied Proteomics in ‘One Health’

“…With regard to studies on identification of biomarkers, Thanomsridetchai et al [ 36 ] proposed proteins that could predict the development of the clinical forms of rabies in affected dogs. These findings were employed by Mehta et al [ 41 ], who worked in animal models and identified 10 proteins (proteoplipid protein 1, glutamate ammonia ligase, calcium calmodulin, dependent kinase 2 alpha, optic atrophy 1, hippocalcin-like protein 4, transgelin 3, adaptor-related protein complex 3, programmed cell death, interacting protein, limbic system associated membrane protein, karyopherin alpha 4). Thereafter, Mehta et al [ 42 ] identified 143 proteins in the neuronal tissues of mice in response to infection and proposed that some molecules, e.g., KPNA4 [ 41 ], could be potential diagnostic markers for the disease.…”

Status of antiviral therapeutics against rabies virus and related emerging lyssaviruses

“…The analysis of the host-RABV interactome has revealed cellular proteins that are essential for completion of the RABV life-cycle and may provide exploitable antiviral target opportunities [80,81]. Targeting of host factors involved in viral replication and pathogenesis offers several advantages over direct-acting antivirals.…”