Hepatitis C as well as ZIKA, both RNA viruses belonging to the Flaviviridae family, are a global health problem with about 130-170 million people chronically infected with HCV and more than 4 million reported cases of ZIKA infections in the Western hemisphere, just in the last 6 months (May 2016). As a first line of defense, complement should help to prevent the establishment of virus infections. However, several pathogens have evolved strategies to evade complement-mediated killing. Therefore we are highly interested in the protection mechanisms of HCV and ZIKA against the complement attack.
Previous studies showed that HCV selectively incorporates CD59, a regulator of complement activation (RCA), while neither CD55 nor CD46 are associated with the virus. While blocking CD59 regulators, about half of the viral titer was reduced meanwhile the rest of HCV particles survived complement-mediated lysis (CML). This indicates that CD59 has an essential contribution to overcome CML, but it also suggest that other complement RCAs may be involved in the regulation process, providing additional resistance.
Therefore, we want to determine whether HCV virions are also able to hijack soluble host RCAs, which could explain the remaining resistance to CML upon CD59 blockade. Furthermore our study should provide detailed information of the incorporation process of CD59 including the time point of acquisition and location of GPI-anchor. Thus our study will not only provide insight into potential evasion mechanisms but might also offer potential therapeutic options by interfering with RCAs on the virus.
Until now very little has been reported about ZIKA in this direction, we hypothesize that also the microcephaly causing virus is able to hijack complement regulators on their surface to protect against CML. These findings could help to better understand the inability of complement to clear a ZIKA infection.
