Genetic Variation of Multiple Serotypes of Enteroviruses Associated with Hand, Foot and Mouth Disease in Southern China

Abstract

Enteroviruses (EVs) species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand, foot and mouth disease (HFMD) in China. Mild infections are common in children; however, HFMD can also cause severe illness that affects the central nervous system. To molecularly characterize EVs, a prospective HFMD virological surveillance program was performed in China between 2013 and 2016. Throat swabs, rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals. EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions (RT-PCRs). Then, the complete VP1 regions of enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16) and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny. Of the 2836 enrolled HFMD patients, 2,517 (89%) were EV positive. The most frequently detected EVs were CVA16 (32.5%, 819), CVA6 (31.2%, 785), and EV-A71 (20.4%, 514). The subgenogroups CVA16_B1b, CVA6_D3a and EV-A71_C4a were predominant in China and recombination was not observed in the VP1 region. Sequence analysis revealed amino acid variations at the 30, 29 and 44 positions in the VP1 region of EV-A71, CVA16 and CVA6 (compared to the respective prototype strains BrCr, G10 and Gdula), respectively. Furthermore, in 21 of 24 (87.5%) identified EV-A71 samples, a known amino acid substitution (D31N) that may enhance neurovirulence was detected. Our study provides insights about the genetic characteristics of common HFMD-associated EVs. However, the emergence and virulence of the described mutations require further investigation. Electronic supplementary material The online version of this article (10.1007/s12250-020-00266-7) contains supplementary material, which is available to authorized users.

Phylogenetics and phylogeographic characteristics of coxsackievirus A16 in hand foot and mouth disease and herpangina cases collected in Beijing, China from 2019 to 2021

“…HFMD typically manifested rashes on the hands, feet, mouth, and buttocks, as well as ulcers and vesicles in the mouth, with or without fever. The primary causative agents of HFMD are members of the species Enterovirus A , including enterovirus A71 (EV‐A71), coxsackievirus A16 (CV‐A16), and coxsackievirus A6 (CV‐A6) 5,7,9–11 . The spectrum of enterovirus causing HFMD and HA cases has changed in recent years in China.…”

“…The primary causative agents of HFMD are members of the species Enterovirus A, including enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and coxsackievirus A6 (CV-A6). 5,7,[9][10][11] The spectrum of enterovirus causing HFMD and HA cases has changed in recent years in China. There has been a significant decrease in EV-A71, while CV-A6 became the dominant serotype, followed by CV-A16, which remains a vital pathogen for HFMD.…”

Effect of difference between EV-A71 virus epidemic strain and “vaccine strain” on neutralizing antibody titer

“…As such, monitoring surveillance of changes within the VP1 region of EVs may allow for the early identification of epidemiological and clinical changes, as well as the identification of potential novel vaccine targets. 48 …”

The Immungenicity and Cross-Neutralizing Activity of Enterovirus 71 Vaccine Candidate Strains

“…In 2004-2005, C4 replaced the B4 sub-genotype as the main genotype in Taiwan [10]. In mainland China, C4 has remained the predominant subgenotype since its first isolation in 1997 [3,11,12].…”