microbeПроблемы особо опасных инфекцийProblems of Particularly Dangerous Infections0370-10692658-719XRussian Research Anti-Plague Institute “Microbe”10.21055/0370-1069-2019-2-6-13microbe-1142Research ArticleОБЗОРЫREVIEWSЛихорадка Зика: разработка средств диагностики, профилактики и леченияZika Fever: Development of Diagnostics, Prevention and TreatmentКазачинскаяЕ. И.KazachinskayaE. I.

630559, Новосибирская обл., р.п. Кольцово

Kol’tsovo, Novosibirsk Region, 630559

alenakaz@vector.nsc.ruШаньшинД. В.Shan’shinD. V.

630559, Новосибирская обл., р.п. Кольцово

Kol’tsovo, Novosibirsk Region, 630559

ИвановаА. В.IvanovaA. V.

630559, Новосибирская обл., р.п. Кольцово

Kol’tsovo, Novosibirsk Region, 630559

ФБУН «Государственный научный центр вирусологии и биотехнологии «Вектор»РоссияState Scientific Centre of Virology and Biotechnology “Vector”Russian Federation20193006201902613Copyright © Казачинская Е.И., Шаньшин Д.В., Иванова А.В., 20192019Казачинская Е.И., Шаньшин Д.В., Иванова А.В.Kazachinskaya E.I., Shan’shin D.V., Ivanova A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.microbe.ru/jour/article/view/1142

Обзор посвящен анализу литературных данных о разрабатываемых средствах диагностики лихорадки Зика и выявления этиологического агента – вируса Зика (ZIKV), относящегося к семейству флавивирусов (Flaviviridae). Рассмотрены также варианты профилактических вакцин и противовирусных препаратов. Метод ОТ-ПЦР имеет решающее значение для подтверждения диагноза лихорадки Зика. РНК ZIKV может быть обнаружена в сыворотке крови, слюне, амниотической и цереброспинальной жидкостях, моче, сперме, вагинальных и цервикальных выделениях. Виремия при лихорадке Зика непродолжительная, в связи с чем присутствие РНК ZIKV в моче и в сперме до 26 и 80 сут соответственно расширяет временной интервал обнаружения этого патогена. Выявление антител класса IgM серологическими методами не является достаточным основанием для подтверждения недавней инфекции, так как антитела этого класса, специфичные к флавивирусам, циркулируют в кровотоке более 12 недель. Диагностическую ценность IgM имеют только для подтверждения врожденной инфекции. Существует проблема дифференциальной диагностики флавивирусных инфекций, вызываемых опасными для человека антигенно-родственными вирусами (например, денге, желтой лихорадки, лихорадки Западного Нила, клещевого и японского энцефалитов) из-за подобия их геномов и, соответственно, схожей антигенной структуры вирусных белков, особенно структурного гликопротеина Е. Более надежные результаты можно получить, используя в качестве антигена для выявления специфических антител неструктурный гликопротеин NS1, полученный методами молекулярной биологии. Этот вирусный белок также может быть использован в серологических тестах в качестве клинического индикатора при острой ЛЗ. При конструировании и исследовании 45 видов кандидатных вакцин (инактивированных, живых аттенуированных, рекомбинантных пептидных, на основе рекомбинантных ДНК и РНК, вирус-векторных и вирусоподобных частиц) против ZIKV установлено, что их защитная эффективность опосредуется индуцированными антителами, специфичными к структурному гликопротеину Е, который инициирует рецепторное связывание и слияние с мембранами инфицируемых клеток. В настоящее время нет ни одного лицензированного средства для лечения пациентов с флавивирусными инфекциями. Ведется скрининг различных препаратов с известной антивирусной активностью и одобренных для применения в клинической практике и поиск новых соединений, ингибирующих проникновение вирусных частиц в клетки хозяина (мишень – структурный гликопротеин Е) и репликацию вируса (мишени – неструктурные белки NS5, NS3, NS2B).

This review is devoted to the analysis of the literature data on the development of tools for diagnostics of Zika fever and detection of etiological agent – Zika virus (ZIKV) belonging to the Flaviviridae family. Preventive vaccines and antiviral drugs are also considered. RT-PCR method is critical for confirmation of Zika fever diagnosis. ZIKV RNA may be detected in blood serum, saliva, amniotic and cerebrospinal fluids, urine, semen, vaginal and cervical secretions. The duration of viremia in case of Zika fever is short; therefore the presence of ZIKV RNA in urine and sperm for up to 26 and 80 days, respectively, extends the time interval for the detection of this pathogen. Detection of IgM antibodies by serological methods is not a good reason to confirm a recent infection, since antibodies of this class, specific to flaviviruses, circulate in the bloodstream for more than 12 weeks. The IgM show high diagnostic value in confirmation of congenital infection only. There is a problem of differential diagnostics of flavivirus infections caused by antigenically related viruses that are dangerous for humans, for instance, Dengue, Yellow fever, West Nile fever viruses, tick-borne and Japanese encephalitis viruses. It is associated with the similarity of their genomes and, consequently, similar antigenic structure of viral proteins, structural glycoprotein E in particular. More reliable results can be obtained by using the nonstructural glycoprotein NS1, produced by molecular biology methods, as an antigen for the detection of specific antibodies. This viral protein can also be used in serological tests, as a clinical indicator in case of acute Zika fever. Forty five types of candidate vaccines against ZIKV, such as inactivated, live attenuated, recombinant, peptide, recombinant DNA and RNA-based, virus-vector and virus-like particle ones were designed and studied. It was established that their protective efficacy is mediated by induced antibodies, specific to structural glycoprotein E which initiates receptor binding and fusion with the membranes of infected cells. Currently, there is no licensed preparation for treating patients with flaviviral infections. Various drugs are screened, both with known antiviral effect and approved for use in clinical practice, and new compounds that inhibit the penetration of viral particles into host cells (structural glycoprotein E being the target) and virus replication (targets are NS5, NS2B nonstructural proteins).

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The authors declare that there are no conflicts of interest present.