Manipulating Adenovirus Hexon Hypervariable Loops Dictates Immune Neutralisation and Coagulation Factor X-dependent Cell Interaction and

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Adenoviruses are mostly considered self-limiting pathogens associated with respiratory, gastrointestinal and ocular infections; however, in immunocompromised subjects disseminated Ad infection can occur with life-threatening consequences. Many human Ads are capable of binding to coagulation factor X (FX). Following intravenous administration in animal models, FX binds directly to the major Ad capsid protein, the hexon, which subsequently results in virus accumulation in the liver. FX coating Ad5 also acts to shield against immune neutralisation via natural IgM antibodies and the classical complement system. Here we show that FX protection is not a conserved mechanism amongst Ads and identify the Ad5 hexon hypervariable regions (HVR) as the capsid proteins targeted by this host defense pathway. Furthermore, we show that genetic inclusion of Ad5 HVRs onto a native non-FX binder Ad26 to be sufficient to confer sensitivity to immune attack in vitro and in vivo. Using intravenous administration, we determine the significance of FX binding to the Ad5-derived HVRs with respect to defending the virus from neutralisation whilst mediating virus tropism. Our study gives new insight into the role of the viral HVRs and of FX at the interface between virus and host defense mechanisms.

Vyšlo v časopise: Manipulating Adenovirus Hexon Hypervariable Loops Dictates Immune Neutralisation and Coagulation Factor X-dependent Cell Interaction and. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004673
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004673

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