Molecular surveillance of coxsackievirus A16 in southern China, 2008-2019.

A national surveillance system on hand, foot, and mouth disease (HFMD) was launched in 2008 in China. Since then, millions of HFMD cases have been reported each year, with enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and coxsackievirus A6 (CV-A6) as the major causative pathogens. Long-term surveillance of viral infection rates and genetic changes is essential for understanding the disease epidemiology pattern. Here, we analyzed molecular surveillance data on CV-A16 covering a period of 12 years (2008-2019) in Guangdong, China, one of the regions reporting the largest number of HFMD cases. Full VP1 sequences of 456 strains were determined to examine the genetic diversity and changes in the distribution of CV-A16 variants. Our study revealed an irregular pattern of CV-A16 infections in Guangdong. Different from the cyclic epidemics observed in some Asia-Pacific regions, there was a continuously high CV-A16 infection rate from 2008 to 2014, and after a period of lower epidemic activity in 2015-2017, an upsurge of CV-A16 infection was observed in 2018-2019. Cocirculation of subgenotypes B1a and B1b was observed, but while subgenotype B1a was predominant from 2008 to 2012, it appears to have been replaced by B1b, which has circulated as the predominant subgenotype since 2013. Phylogenetic analysis showed that most of the circulating CV-A16 strains are endemic, with occasional transmission between neighboring regions. The re-emergence of B1a in 2016-2019 in Guangdong was likely the result of introduction(s) from Southeast Asia. These results highlight the importance of continuous molecular surveillance from different areas, which will improve our understanding of the origin of the epidemic and facilitate the development of strategies for HFMD disease control.

Claudin-2 downregulation by KSHV infection is involved in the regulation of endothelial barrier function.

BACKGROUND: Kaposi sarcoma (KS), caused by the infection of Kaposi sarcoma-associated herpesvirus (KSHV), is a disease manifested mainly by dark purple skin and mouth nodules. Cancer care studies showed that co-infection of KSHV and human immunodeficiency virus (HIV) was able to increase the patients' survival, but the underlying mechanisms are still elusive. METHODS: To understand the mechanism underlying the prolonged survival in KSHV-HIV co-infected patients, we performed microarray analysis on RNA extracted from biopsies from KS tumors and adjacent healthy tissues in four KS patients. Subsequently, we performed hierarchical clustering, gene ontology (GO) and ingenuity pathway analysis. We then characterized the roles of tight junction protein claudin-2 in the endothelial barrier function. RESULTS: Three hundred and forty-three differentially expressed genes were identified, of which 246 genes exhibited significantly increased expression in the tumor compared to the adjacent healthy tissue and 97 genes showed downregulated expression, including claudin-2. Knockdown of claudin-2 in cultured endothelial cells enhances barrier function by altering the charge selectivity, but not the size selectivity. CONCLUSION: Claudin-2 expression is decreased in KS tumors from patients co-infected with KSHV and HIV. Decreased claudin-2 enhances endothelial barrier function and may play a role in the prolonged survival of patients with KSHV and HIV co-infection.

[Epidemiology Characteristics and Pathogen Surveillance of Hand, Foot and Mouth Disease in Guangdong Province, China, 2008～2015].

To understand the epidemiological etiology characteristics of hand, foot and mouth disease(HFMD)in Guangdong province, and to explore the risk change trend of the whole province. By using the descriptive epidemiological methods, the whole province's incidence trend, population distribution and pathogenic form of HFMD were analyzed with the HFMD surveillance data,population data and geographic information of Guangdong province from 2008 to 2015.The analysis results show: A total of 2,133,722 cases of HFMD, including 5,066 severe cases and 259 death cases were reported in Guangdong province from 2008 to 2015.All the cities of Guangdong had HFMD cases, especially the Pearl River Delta Regions, which were on high-risk areas. There were two peaks every year, with the main peak of incidence occurred in spring and summer, and the sub peak occurred in autumn.Most cases were children aged<5years old, the proportion of this group in overall infections, the severe and death cases were 90.58%,95.93%and 97.30%,respectively,while the proportion for the children less than 3years old were 77.32% and 81.85%,respectively. The incidence of this disease among men was higher than that of women. Dynamic changes were presented between different years and seasons:CV-A16 was more popular in 2009,and enterovirus that none EV-A71 and none CV-A16 were predominant strains in 2013 and 2015.Especially in 2015,the proportion of other EV ranged as high as 71.97%.Besides,EV-A71 was the absolute predominance pathogen within death cases and was important pathogen in severe cases. This study suggests that HFMD epidemiology and laboratory monitoring in Guangdong Province should be strengthened, and provides scientific data support for further improvement of HFMD prevention and control strategies in Guangdong Province.

The Epidemiological Study of Coxsackievirus A6 revealing Hand, Foot and Mouth Disease Epidemic patterns in Guangdong, China.

Enterovirus A71 (EVA71) and Coxsackievirus A16 (CVA16) are regarded as the two major causative pathogens in hand, foot and mouth disease (HFMD) epidemics. However, CVA6, previously largely ignored, became the predominant pathogen in China in 2013. In this study, we describe the epidemiological trends of CVA6 during the annual HFMD outbreaks from 2008 to 2013 in Guangdong, China. The study results show that CVA6 has been one of three major causative agents of HFMD epidemics since 2009. The periodic rotation and dominance of the three pathogens, EVA71, CVA16 and CVA6, may have contributed to the continuously increasing HFMD epidemics. Moreover, phylogenetic analysis of the VP1 gene shows that major circulating CVA6 strains collected from 2009 to 2013 are distinct from the earlier strains collected before 2009. In conclusion, the discovery from this research investigating epidemiological trends of CVA6 from 2008 to 2013 explains the possible pattern of the continuous HFMD epidemic in China. The etiological change pattern also highlights the need for improvement for pathogen surveillance and vaccine strategies for HFMD control in China.