Utility of Proteomics in Emerging and Re-Emerging Infectious Diseases Caused by RNA Viruses

Abstract

Emerging and re-emerging infectious diseases due to RNA viruses cause major negative consequences for the quality of life, public health, and overall economic development. Most of the RNA viruses causing illnesses in humans are of zoonotic origin. Zoonotic viruses can directly be transferred from animals to humans through adaptation, followed by human-to-human transmission, such as in human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and, more recently, SARS coronavirus 2 (SARS-CoV-2), or they can be transferred through insects or vectors, as in the case of Crimean-Congo hemorrhagic fever virus (CCHFV), Zika virus (ZIKV), and dengue virus (DENV). At the present, there are no vaccines or antiviral compounds against most of these viruses. Because proteins possess a vast array of functions in all known biological systems, proteomics-based strategies can provide important insights into the investigation of disease pathogenesis and the identification of promising antiviral drug targets during an epidemic or pandemic. Mass spectrometry technology has provided the capacity required for the precise identification and the sensitive and high-throughput analysis of proteins on a large scale and has contributed greatly to unravelling key protein–protein interactions, discovering signaling networks, and understanding disease mechanisms. In this Review, we present an account of quantitative proteomics and its application in some prominent recent examples of emerging and re-emerging RNA virus diseases like HIV-1, CCHFV, ZIKV, and DENV, with more detail with respect to coronaviruses (MERS-CoV and SARS-CoV) as well as the recent SARS-CoV-2 pandemic.

Top-Down and Bottom-Up Proteomics Methods to Study RNA Virus Biology

“…Recently, global efforts to systematically profile cellular targets of viral proteins have intensified exponentially, greatly expanding the virus–host interaction landscape. Using ectopically expressed viral proteins as baits, multiple studies profiled the interactome of entire viral species including DENV, ZIKV, Ebola or Influenza virus (reviewed in [ 134 ]). For instance, by using label-free LC-MS/MS, multiple independent groups profiled the global cellular interactome of ZIKV in vertebrate and invertebrate cells, identifying cellular proteins with roles in ZIKV-induced neurodevelopmental defects [ 11 , 135 , 136 ].…”

Mass spectrometry-based proteomics in basic and translational research of SARS-CoV-2 coronavirus and its emerging mutants

“…It should be noted that one of the first proteomic studies on SARS-related proteins was conducted in 2003 and revealed NCAP_SARS protein as a major immunogen [ 25 ]. Interestingly, a caspase cleavage motif (responsible for the virus proteolysis and elimination by the host cells caspases) was present in all previous coronavirus nucleoproteins [ 27 ], but not in SARS-COV-1 [ 25 ]. Dysregulation of PI3K/AKT pathway was identified in both SARS-CoV-2 and SARS-CoV-1 [ 28 ].…”

Herramientas biotecnológicas en el diagnóstico, prevención y tratamiento frente a pandemias

“…Las tecnologías "omicas" inspiradas en el proceso natural de producción de biomoléculas en las células, han aportado significativamente en el avance del diagnóstico, manejo y pronóstico de varias enfermedades, siendo elementales para el perfeccionamiento de la medicina personalizada de próxima generación 180,181 , debido a que permiten una mejor comprensión de los mecanismos moleculares y celulares que interfieren en la progresión de una enfermedad en humanos 180 . Entre las "ómicas" con mayor avance están la genómica, transcriptómica, proteómica y metabolómica 181 , siendo la genómica y proteómica las "omicas", con un protagonismo superior en la investigación de diagnóstico y tratamiento en enfermedades infecciosas 182 . La genómica trata de la estructura, función, evolución y mapeo de genomas, con el objetivo de cuantificar y caracterizar genes 180 .…”

“…La proteómica, por otro lado, estudia todas las proteínas presentes en una célula, tejido u organismo, centrándose en las propiedades bioquímicas, roles funcionales y sus cambios frente al crecimiento o a estímulos internos y externos 182,187,188 . La proteómica a través de espectrometría de masas facilita los análisis de precisión, sensibles y de alto rendimiento de proteínas a gran escala 187 .…”

“…La proteómica a través de espectrometría de masas facilita los análisis de precisión, sensibles y de alto rendimiento de proteínas a gran escala 187 . Además, es posible comprender y descubrir interacciones claves proteína-proteína, redes de señalización, interacciones complejas huésped-patógeno, respuestas del huésped al invasor y los mecanismos de aprovechamiento del microorganismo, lo que ha proporcionado información sobre la patogénesis de una enfermedad, caracterización de biomarcadores para métodos de diagnóstico y fármacos antivirales durante una epidemia 182,188 . Al mismo tiempo el prototipado por espectrometría de masas puede ser un método de diagnóstico alternativo 188 .…”