Background:Hand,foot and mouth disease(HFMD)is a common infectious disease caused by viral infection by a variety of enteroviruses,with coxsackievirus A 10(CA10)having become more prevalent in recent years.Methods:In ...Background:Hand,foot and mouth disease(HFMD)is a common infectious disease caused by viral infection by a variety of enteroviruses,with coxsackievirus A 10(CA10)having become more prevalent in recent years.Methods:In this study,models of CA10 infection were established in 7-day-old Institute of Cancer Research(ICR)mice by intraperitoneal injection to analyze the pathogenicity of the virus.RNA sequencing analysis was used to screen the differentially expressed genes(DEGs)after CA10 infection.Coxsackievirus A 16(CA16)and enterovirus 71(EV71)infections were also compared with CA10.Results:After CA10 virus infection,the mice showed paralysis of the hind limbs at 3 days post infection and weight loss at 5 days post infection.We observed viral replication in various tissues and severe inflammatory cell infiltration in skeletal muscle.The RNA-sequencing analysis showed that the DEGs in blood,muscle,thymus and spleen showed heterogeneity after CA10 infection and the most upregulated DEGs in muscle were enriched in immune-related pathways.Compared with CA16 and EV71 infection,CA10 may have an inhibitory effect on T helper(Th)cell differentiation and cell growth.Additionally,the common DEGs in the three viruses were most enriched in the immune system response,including the Toll-l ike receptor pathway and the nucleotide-binding and oligomerization domain(NOD)-l ike pathway.Conclusions:Our findings revealed a group of genes that coordinate in response to CA10 infection,which increases our understanding of the pathological mechanism of HFMD.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2022YFC2303404)the CAMS Innovation Fund for Medical Sciences(CIFMS)grant(2021-1-I2 M-035,2022-I2M-1-020)。
文摘Background:Hand,foot and mouth disease(HFMD)is a common infectious disease caused by viral infection by a variety of enteroviruses,with coxsackievirus A 10(CA10)having become more prevalent in recent years.Methods:In this study,models of CA10 infection were established in 7-day-old Institute of Cancer Research(ICR)mice by intraperitoneal injection to analyze the pathogenicity of the virus.RNA sequencing analysis was used to screen the differentially expressed genes(DEGs)after CA10 infection.Coxsackievirus A 16(CA16)and enterovirus 71(EV71)infections were also compared with CA10.Results:After CA10 virus infection,the mice showed paralysis of the hind limbs at 3 days post infection and weight loss at 5 days post infection.We observed viral replication in various tissues and severe inflammatory cell infiltration in skeletal muscle.The RNA-sequencing analysis showed that the DEGs in blood,muscle,thymus and spleen showed heterogeneity after CA10 infection and the most upregulated DEGs in muscle were enriched in immune-related pathways.Compared with CA16 and EV71 infection,CA10 may have an inhibitory effect on T helper(Th)cell differentiation and cell growth.Additionally,the common DEGs in the three viruses were most enriched in the immune system response,including the Toll-l ike receptor pathway and the nucleotide-binding and oligomerization domain(NOD)-l ike pathway.Conclusions:Our findings revealed a group of genes that coordinate in response to CA10 infection,which increases our understanding of the pathological mechanism of HFMD.