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The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis.

ABSTRACT: Zika virus was discovered ?70 years ago in Uganda and maintained a low profile as a human disease agent in Africa and Asia. Only recently has it caused explosive outbreaks in previously unaffected regions, first in Oceania and then in the Americas since 2015. Of special concern is the newly identified link between congenital malformations (especially microcephaly) and Zika virus infections during pregnancy. At present, it is unclear whether Zika virus changed its pathogenicity or whether the huge number of infections allowed the recognition of a previously cryptic pathogenic property. The purpose of this review is to discuss recent data on the molecular antigenic structure of Zika virus in the context of antibody-mediated neutralization and antibody-dependent enhancement (ADE) of infection, a phenomenon that has been implicated in the development of severe disease caused by the related dengue viruses. Emphasis is given to epitopes of antibodies that potently neutralize Zika virus and also to epitopes that provide antigenic links to other important human-pathogenic flaviviruses such as dengue, yellow fever, West Nile, Japanese encephalitis, and tick-borne encephalitis viruses. The antigenic cross talk between Zika and dengue viruses appears to be of special importance, since they cocirculate in many regions of endemicity and sequential infections are likely to occur frequently. New insights into the molecular antigenic structure of Zika virus and flaviviruses in general have provided the foundation for great progress made in developing Zika virus vaccines and antibodies for passive immunization.

SUBMITTER: Heinz FX

PROVIDER: S-EPMC5312239 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis.

Heinz Franz X FX Stiasny Karin K

Microbiology and molecular biology reviews : MMBR 20170208 1

Zika virus was discovered ∼70 years ago in Uganda and maintained a low profile as a human disease agent in Africa and Asia. Only recently has it caused explosive outbreaks in previously unaffected regions, first in Oceania and then in the Americas since 2015. Of special concern is the newly identified link between congenital malformations (especially microcephaly) and Zika virus infections during pregnancy. At present, it is unclear whether Zika virus changed its pathogenicity or whether the hug ...[more]

PMID: 28179396

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Project description:BackgroundZika virus (ZIKV) infection has potential result in severe birth effects. An improved understanding of global trend and regional differences is needed.MethodsAnnual ZIKV infection episodes and incidence rates were collected from Global Burden of Disease Study 2019. Episodes changes and estimated annual percentage changes (EAPCs) of age-standardized incidence rate (ASR) were calculated. Top passenger airport-pairs were obtained from the International Air Transport Association to understand places susceptible to imported ZIKV cases.ResultsGlobally, the ASR increased by an average of 72.85% (95%CI: 16.47% to 156.53%) per year from 2011 to 2015 and subsequently decreased from 20.25 per 100,000 in 2015 to 3.44 per 100,000 in 2019. Most of ZIKV infections clustered in Latin America. The proportion of episodes in Central and Tropical Latin America decreased in 2019 with sporadic episodes elsewhere. High Socio-Demographic Index (SDI) regions had more episodes in 2019 than in 2015. Additionally, 15-49 years group had the largest proportion of episodes, females had a higher number of episodes, and a higher incidence rate of 70 plus group was observed in males than females. Certain cities in Europe, North America and Latin America/Caribbean had a high population mobility in ZIKV outbreak areas considered a high risk of imported cases.ConclusionsZIKV infection is still a public health threat in Latin America and Caribbean and high SDI regions suffered an increasing trend of ZIKV infection. Interventions such as development of surveillance networks and vector-control should be attached to ZIKV control in these key regions. Reproductive suggestions should be taken to reduce ZIKV-related birth defects for the people of reproductive age who are facing a higher threat of ZIKV infection, especially females. Moreover, surveillance of travellers is needed to reverse the uptrends of travel-related imported ZIKV infection. More studies focusing on ZIKV should be performed to make targeted and effective prevention strategies in the future.

Project description:BackgroundHealth authorities in the United States and Europe reported an increasing number of travel-associated episodes of sexual transmission of Zika virus (ZIKV) following the 2015-2017 ZIKV outbreak. This, and other scientific evidence, suggests that ZIKV is sexually transmissible in addition to having its primary mosquito-borne route. The objective of this systematic review and evidence synthesis was to clarify the epidemiology of sexually transmitted ZIKV.Methods and findingsWe performed a living (i.e., continually updated) systematic review of evidence published up to 15 April 2018 about sexual transmission of ZIKV and other arthropod-borne flaviviruses in humans and other animals. We defined 7 key elements of ZIKV sexual transmission for which we extracted data: (1) rectal and vaginal susceptibility to infection, (2) incubation period following sexual transmission, (3) serial interval between the onset of symptoms in a primary and secondary infected individuals, (4) duration of infectiousness, (5) reproduction number, (6) probability of transmission per sex act, and (7) transmission rate. We identified 1,227 unique publications and included 128, of which 77 presented data on humans and 51 presented data on animals. Laboratory experiments confirm that rectal and vaginal mucosae are susceptible to infection with ZIKV and that the testis serves as a reservoir for the virus in animal models. Sexual transmission was reported in 36 human couples: 34/36 of these involved male-to-female sexual transmission. The median serial symptom onset interval in 15 couples was 12 days (interquartile range: 10-14.5); the maximum was 44 days. We found evidence from 2 prospective cohorts that ZIKV RNA is present in human semen with a median duration of 34 days (95% CI: 28-41 days) and 35 days (no CI given) (low certainty of evidence, according to GRADE). Aggregated data about detection of ZIKV RNA from 37 case reports and case series indicate a median duration of detection of ZIKV of 40 days (95% CI: 30-49 days) and maximum duration of 370 days in semen. In human vaginal fluid, median duration was 14 days (95% CI: 7-20 days) and maximum duration was 37 days (very low certainty). Infectious virus in human semen was detected for a median duration of 12 days (95% CI: 1-21 days) and maximum of 69 days. Modelling studies indicate that the reproduction number is below 1 (very low certainty). Evidence was lacking to estimate the incubation period or the transmission rate. Evidence on sexual transmission of other flaviviruses was scarce. The certainty of the evidence is limited because of uncontrolled residual bias.ConclusionsThe living systematic review and sexual transmission framework allowed us to assess evidence about the risk of sexual transmission of ZIKV. ZIKV is more likely transmitted from men to women than from women to men. For other flaviviruses, evidence of sexual transmissibility is still absent. Taking into account all available data about the duration of detection of ZIKV in culture and from the serial interval, our findings suggest that the infectious period for sexual transmission of ZIKV is shorter than estimates from the earliest post-outbreak studies, which were based on reverse transcription PCR alone.

Project description:The Flavivirus genus comprises several human pathogens such as dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV). Although ZIKV usually causes mild symptoms, growing evidence is linking it to congenital birth defects and to increased risk of Guillain-Barré syndrome. ZIKV encodes a polyprotein that is processed to produce three structural and seven nonstructural (NS) proteins. We investigated the evolution of the viral polyprotein in ZIKV and in related flaviviruses (DENV, Spondweni virus, and Kedougou virus). After accounting for saturation issues, alignment uncertainties, and recombination, we found evidence of episodic positive selection on the branch that separates DENV from the other flaviviruses. NS1 emerged as the major selection target, and selected sites were located in immune epitopes or in functionally important protein regions. Three of these sites are located in an NS1 region that interacts with structural proteins and is essential for virion biogenesis. Analysis of the more recent evolutionary history of ZIKV lineages indicated that positive selection acted on NS5 and NS4B, this latter representing the preferential target. All selected sites were located in the N-terminal portion of NS4B, which inhibits interferon response. One of the positively selected sites (26M/I/T/V) in ZIKV also represents a selection target in sylvatic DENV2 isolates, and a nearby residue evolves adaptively in JEV. Two additional positively selected sites are within a protein region that interacts with host (e.g. STING) and viral (i.e. NS1, NS4A) proteins. Notably, mutations in the NS4B region of other flaviviruses modulate neurovirulence and/or neuroinvasiveness. These results suggest that the positively selected sites we identified modulate viral replication and contribute to immune evasion. These sites should be prioritized in future experimental studies. However, analyses herein detected no selective events associated to the spread of the Asian/American ZIKV lineage.

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The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis.

Publications

The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis.

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