Abstract
Enterovirus 71 (EV71) is the major pathogen responsible for fatal hand, foot and mouth disease (HFMD). Our previous work reported on an EV71-infected rhesus monkey infant model that presented with histo-pathologic changes of the central nervous system (CNS) and lungs. This study is focused on the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs) from EV71-infected rhesus monkey infants. The expression of more than 500 functional genes associated with multiple pathways was modulated. The expression of genes associated with immune inflammatory responses was up-regulated during the period from days 4 to 10 post-infection. The expression of two genes (TAC1 and IL17A), which play major roles in inflammatory reactions, was remarkably up-regulated during the infection period. Furthermore, a higher expression level of the TAC1 gene was identified in the CNS compared to the lungs, but a high expression level of the IL-17A gene was observed in the lungs and not in the CNS. The results of this study suggest at least two facts about EV71 infection, which are that: the TAC1 gene that encodes substance P and neurokinin-A is present in both PBMCs and the hypothalamus; and the up-regulation of IL-17A is sustained in the peripheral blood.
Highlights
Pathogenic studies focusing on hand, foot and mouth disease (HFMD) and its emerging epidemics in the Asia-Pacific regions in recent years have demonstrated that enterovirus 71 (EV71) is one of the major pathogens responsible for human cases of HFMD, and infection with this virus occasionally leads to severe diseases and death [1,2]
Multiple clinical and pathological studies focusing on the fatal cases of HFMD suggest that the brainstem encephalitis caused by EV71 infection of the central nervous system (CNS) and the subsequent neurogenic heart and lung failure contribute to the severe pathogenesis in these human patients [3,4,5]
Our results showed a marked variety of gene expression profiles in the peripheral blood mononuclear cells (PBMCs) of EV71-infected rhesus infants during the pathogenic process, and these profiles were characterized by the activation of the integral functions of the immune system, as well as the up-regulation of genes associated with the inflammatory response
Summary
Pathogenic studies focusing on hand, foot and mouth disease (HFMD) and its emerging epidemics in the Asia-Pacific regions in recent years have demonstrated that enterovirus 71 (EV71) is one of the major pathogens responsible for human cases of HFMD, and infection with this virus occasionally leads to severe diseases and death [1,2]. Multiple clinical and pathological studies focusing on the fatal cases of HFMD suggest that the brainstem encephalitis caused by EV71 infection of the central nervous system (CNS) and the subsequent neurogenic heart and lung failure contribute to the severe pathogenesis in these human patients [3,4,5]. The basic EV71 pathogenic process was successfully mimicked in rhesus monkey infant [11].These monkeys exhibited the typical clinical manifestations, such as vesicles on the mucosa of the palate, tongue and limbs; fever;and the histopathological manifestations, such as a variety of viral loads, antigen expression and perivascular infiltration in the CNS [3,11] While such a pathogenic process did not result in severe neurogenic heart failure or pulmonary edema, there was remarkable alveolar inflammatory effusion and partial destruction of the alveolar wall, among other pathological changes [3,11]. The presence of these functional molecules in the major organs and tissues targeted by viral infection suggests their potential significance in the pathogenic process of EV71 infection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
