Lights and Shadows of TORCH Infection Proteomics

Abstract

Congenital abnormalities cause serious fetal consequences. The term TORCH is used to designate the most common perinatal infections, where: (T) refers to toxoplasmosis, (O) means "others" and includes syphilis, varicella-zoster, parvovirus B19, zika virus (ZIKV), and malaria among others, (R) refers to rubella, (C) relates to cytomegalovirus infection, and (H) to herpes simplex virus infections. Among the main abnormalities identified in neonates exposed to congenital infections are central nervous system (CNS) damage, microcephaly, hearing loss, and ophthalmological impairment, all requiring regular follow-up to monitor its progression. Protein changes such as mutations, post-translational modifications, abundance, structure, and function may indicate a pathological condition before the onset of the first symptoms, allowing early diagnosis and understanding of a particular disease or infection. The term “proteomics” is defined as the science that studies the proteome, which consists of the total protein content of a cell, tissue or organism in a given space and time, including post-translational modifications (PTMs) and interactions between proteins. Currently, quantitative bottom-up proteomic strategies allow rapid and high throughput characterization of complex biological mixtures. Investigating proteome modulation during host–pathogen interaction helps in elucidating the mechanisms of infection and in predicting disease progression. This “molecular battle” between host and pathogen is a key to identify drug targets and diagnostic markers. Here, we conducted a survey on proteomic techniques applied to congenital diseases classified in the terminology “TORCH”, including toxoplasmosis, ZIKV, malaria, syphilis, human immunodeficiency virus (HIV), herpes simplex virus (HSV) and human cytomegalovirus (HCVM). We have highlighted proteins and/or protein complexes actively involved in the infection. Most of the proteomic studies reported have been performed in cell line models, and the evaluation of tissues (brain, muscle, and placenta) and biofluids (plasma, serum and urine) in animal models is still underexplored. Moreover, there are a plethora of studies focusing on the pathogen or the host without considering the triad mother-fetus-pathogen as a dynamic and interconnected system.

Proteomic profiles of Zika virus‐infected placentas bearing fetuses with microcephaly

“…Proteomics is a powerful tool to study the pathogenicity of the virus. The development of new sample fractionation techniques, high‐throughput MS‐based methods, and bioinformatics analyses of the data allows a global understanding of the changes that occur after virus infection [21]. Using affinity purification coupled to mass spectrometry analysis (AP‐MS) Scaturro et al.…”

Neurodevelopmental outcomes in congenital and perinatal infections

“…The mechanisms by which these pathogens evade the maternal-placental defense systems and cause fetal brain disease are complex, involving hostpathogen immune interactions and nonimmune changes [36,37]. Many pathogens can invade and infect placental cells [38].…”

Recent advances in genetic etiology of non-syndromic deafness in children

“…Infectious viruses commonly transmitted to the fetus through teratogenic effects include TORCH (Toxoplasmosis-Other-Rubella-Cytomegalovirus-Herpes Simplex) ( Nance, 2003 ). Among these, congenital hearing loss can be attributed to cytomegalovirus, rubella, herpes simplex, lymphocytic choroidal meningitis, and Zika virus infections ( Macedo-da-Silva et al, 2020 ). Other environmental factors occurring at or after birth that can lead to hearing loss include hypoxia, prematurity, complications related to Rh factors in the blood, and bacterial meningitis.…”