Genetic and Cross Neutralization Analyses of Coxsackievirus A16 Circulating in Taiwan from 1998 to 2021 Suggest Dominant Genotype B1 can Serve as Vaccine Candidate

Abstract

Coxsackievirus A16 (CVA16) is well known for causing hand-foot-and-mouth disease (HFMD) and outbreaks were frequently reported in Taiwan in the past twenty years. The epidemiology and genetic variations of CVA16 in Taiwan from 1998 to 2021 were analyzed in this study. CVA16 infections usually occurred in early summer and early winter, and showed increased incidence in 1998, 2000–2003, 2005, 2007–2008, and 2010 in Taiwan. Little or no CVA16 was detected from 2017 to 2021. CVA16 infection was prevalent in patients between 1 to 3 years old. A total of 69 isolates were sequenced. Phylogenetic analysis based on the VP1 region showed that CVA16 subgenotype B1 was dominantly isolated in Taiwan from 1998 to 2019, and B2 was identified only from isolates collected in 1999 and 2000. There was a high frequency of synonymous mutations in the amino acid sequences of the VP1 region among CVA16 isolates, with the exception of position 145 which showed positive selection. The recombination analysis of the whole genome of CVA16 isolates indicated that the 5′-untranslated region and the non-structural protein region of CVA16 subgenotype B1 were recombined with Coxsackievirus A4 (CVA4) and enterovirus A71 (EVA71) genotype A, respectively. The recombination pattern of subgenotype B2 was similar to B1, however, the 3D region was similar to EVA71 genotype B. Cross-neutralization among CVA16 showed that mouse antisera from various subgenotypes viruses can cross-neutralize different genotype with high neutralizing antibody titers. These results suggest that the dominant CVA16 genotype B1 can serve as a vaccine candidate for CVA16.

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

“…Coxsackievirus A16 (CV‐A16) is a single‐stranded RNA virus belonging to the family Picornaviridae , genus Enterovirus , and species Enterovirus A according to the International Committee on Taxonomy of Viruses (ICTV) 1 . Since its first discovery in South Africa in 1951, CV‐A16 has been widely prevalent globally, especially in the Asia‐Pacific region, 2 including Taiwan, 3 Guangdong, 4 Singapore, 5 Malaysia, 6 and Vietnam 7 . It is the primary pathogen responsible for causing hand, foot, and mouth disease (HFMD) and Herpangina (HA), and can sometimes lead to severe complications such as encephalitis, aseptic meningitis, acute flaccid paralysis, mycocarditis, and others 8 .…”

EV71 5’UTR interacts with 3D protein affecting replication through the AKT-mTOR pathway

“…EV71 is one of the pathogens of hand, foot and mouth disease, which can cause nervous system complications. In recent years, HFMD has broken out frequently in many countries and regions, posing a huge threat to public health security [27][28][29][30]. Most studies only focus on the structure and function of a single functional region of EV71, resulting in little attention to the interaction between multiple domains in the viral genome.…”

Molecular evolutionary dynamics of enterovirus A71, coxsackievirus A16 and coxsackievirus A6 causing hand, foot and mouth disease in Thailand, 2000–2022

“…The CVA16 Thailand viruses were phylogenetically related to those reported in China and Vietnam 15 . Likewise, the CVA16 B1 was also the predominant genotype for HFMD cases in China from 2000 to 2018 5 , 6 , 46 , and it is a recommended candidate for vaccine development 47 . On the other hand, HFMD outbreaks caused by CVA6 were more frequent in several countries in Europe, Northern America, and Asia 48 .…”