Flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV) are spread by mosquitoes and cause human disease and mortality in tropical areas. In contrast, Powassan virus (POWV), which causes severe neurologic illness, is a flavivirus transmitted by ticks in temperate regions of the Northern hemisphere. We find serologic neutralizing activity against POWV in individuals living in Mexico and Brazil. Monoclonal antibodies P002 and P003, which were derived from a resident of Mexico (where POWV is not reported), neutralize POWV lineage I by recognizing an epitope on the virus envelope domain III (EDIII) that is shared with a broad range of tick- and mosquito-borne flaviviruses. Our findings raise the possibility that POWV, or a flavivirus closely related to it, infects humans in the tropics.
- MeSH
- epitopy imunologie MeSH
- Flavivirus imunologie MeSH
- klíšťata virologie imunologie MeSH
- lidé MeSH
- monoklonální protilátky imunologie MeSH
- neutralizující protilátky * imunologie MeSH
- protilátky virové imunologie MeSH
- viry klíšťové encefalitidy imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Brazílie MeSH
- Mexiko MeSH
Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC50s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI-EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.
- MeSH
- analýza přežití MeSH
- epitopy imunologie MeSH
- imunoglobulin G aplikace a dávkování imunologie MeSH
- klíšťová encefalitida imunologie prevence a kontrola virologie MeSH
- kohortové studie MeSH
- kultivované buňky MeSH
- lidé MeSH
- monoklonální protilátky aplikace a dávkování genetika imunologie MeSH
- myši inbrední BALB C MeSH
- neutralizující protilátky aplikace a dávkování genetika imunologie MeSH
- proteiny virového obalu genetika imunologie MeSH
- protilátky virové aplikace a dávkování genetika imunologie MeSH
- sekvence aminokyselin MeSH
- sekvenční homologie aminokyselin MeSH
- viry klíšťové encefalitidy účinky léků imunologie fyziologie MeSH
- zkřížené reakce imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
