Molecular phylogeny of coxsackievirus A16.
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ABSTRACT:
SUBMITTER: Sun T
PROVIDER: S-EPMC4187763 | biostudies-literature | 2014 Oct
REPOSITORIES: biostudies-literature
Publications
Molecular phylogeny of coxsackievirus A16.
Sun Ting T Liu Yiming Y Zhang Yanjun Y Zhou Linfu L
Journal of clinical microbiology 20141001 10
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Project description:The hand, foot and mouth disease (HFMD) epidemics have mainly been caused by human enterovirus 71 and human coxsackievirus A16 (CA16), which circulated alternatively or together in the epidemic area. The aim of the present study was to provide guidance in the prevention and control of HFMD from CA16 infection. The molecular epidemiology of the human CA16 strains was investigated. Overall, 1,151 specimens (throat swabs) were collected from 1,151 patients with HFMD symptoms. The results of the homology comparison in the VP1 of CA16 strains showed that the CA16 strains belonged to the B1b subgenotype. The difference of the 6 CA16 strains analyzed showed that the most prominent strain was the A genotype, and the most close strains were the B1 gene subtype, particularly the B1b gene subtype. With regards to the amino acids, in addition to the A genotype, the differences of amino acids with other gene subtype was not significant. The present data suggest that more effective and highly targeted intervention mechanisms could be developed for the prevention and control of HFMD.
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Project description:Coxsackievirus A16 (CVA16) causes hand, foot and mouth disease in infants and young children. However, no vaccine or anti-viral agent is currently available for CVA16. Here, the functions and working mechanisms of two CVA16-specific neutralizing monoclonal antibodies (MAbs), 9B5 and 8C4, are comprehensively investigated. Both 9B5 and 8C4 display potent neutralization in vitro and prophylactic and therapeutic efficacy in a mouse model of CVA16 infection. Mechanistically, 9B5 exerts neutralization primarily through inhibiting CVA16 attachment to cell surface via blockade of CVA16 binding to its attachment receptor, heparan sulfate, whereas 8C4 functions mainly at the post-attachment stage of CVA16 entry by interfering with the interaction between CVA16 and its uncoating receptor SCARB2. Cryo-EM studies show that 9B5 and 8C4 target distinct epitopes located at the 5-fold and 3-fold protrusions of CVA16 capsids, respectively, and exhibit differential binding preference to three forms of naturally occurring CVA16 particles. Moreover, 9B5 and 8C4 are compatible in formulating an antibody cocktail which displays the ability to prevent virus escape seen with individual MAbs. Together, our work elucidates the functional and structural basis of CVA16 antibody-mediated neutralization and protection, providing important information for design and development of effective CVA16 vaccines and antibody therapies.
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Project description:Background: Hand, Foot and Mouth Disease (HFMD) is a major public health concern in the Asia-Pacific region. Most recent HFMD outbreaks have been caused by enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), CVA10, and CVA6. There has been no report regarding the epidemiology and genetic diversity of CVA16 in Vietnam. Such knowledge is critical to inform the development of intervention strategies. Materials and Methods: From 2011 to 2017, clinical samples were collected from in- and outpatients enrolled in a HFMD research program conducted at three referral hospitals in Ho Chi Minh City (HCMC), Vietnam. Throat or rectal swabs positive for CVA16 with sufficient viral load were selected for whole genome sequencing and evolutionary analysis. Results: Throughout the study period, 320 CVA16 positive samples were collected from 2808 HFMD patients (11.4%). 59.4% of patients were male. The median age was 20.8 months (IQR, 14.96-31.41). Patients resided in HCMC (55.3%), Mekong Delta (22.2%), and South East Vietnam (22.5%). 10% of CVA16 infected patients had moderately severe or severe HFMD. CVA16 positive samples from 153 patients were selected for whole genome sequencing, and 66 complete genomes were obtained. Phylogenetic analysis demonstrated that Vietnamese CVA16 strains belong to a single genogroup B1a that clusters together with isolates from China, Japan, Thailand, Malaysia, France and Australia. The CVA16 strains of the present study were circulating in Vietnam some 4 years prior to its detection in HFMD cases. Conclusion: We report for the first time on the molecular epidemiology of CVA16 in Vietnam. Unlike EV-A71, which showed frequent replacement between subgenogroups B5 and C4 every 2-3 years in Vietnam, CVA16 displays a less pronounced genetic alternation with only subgenogroup B1a circulating in Vietnam since 2011. Our collective findings emphasize the importance of active surveillance for viral circulation in HFMD endemic countries, critical to informing outbreak response and vaccine development.
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