Exploitation of the Complement System by Oncogenic Kaposi's Sarcoma-Associated Herpesvirus for Cell Survival and Persistent Infection

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The complement system is an important part of the innate immune system. Pathogens have evolved diverse strategies to evade host immune responses including attack of the complement system. Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with Kaposi's sarcoma (KS), primary effusion lymphoma and a subset of multicentric Castleman's disease. KSHV encodes a number of viral proteins to counter host immune responses during productive lytic replication. On the other hand, KSHV utilizes latency as a default replication program during which it expresses a minimal number of proteins to evade host immune detection. Thus, the complement system is expected to be silent during KSHV latency. In this study, we have found that the complement system is unexpectedly activated in latently KSHV-infected endothelial cells and in KS tumor cells wherein KSHV downregulates the expression of CD55 and CD59 complement regulatory proteins. More interestingly, most of latently KSHV-infected cells not only are resistant to complement-mediated cell killing, but also acquire survival advantage by inducing STAT3 tyrosine phosphorylation. These results demonstrate a novel mechanism by which an oncogenic virus exploits the host innate immune system to promote viral persistent infection.

Vyšlo v časopise: Exploitation of the Complement System by Oncogenic Kaposi's Sarcoma-Associated Herpesvirus for Cell Survival and Persistent Infection. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004412
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004412

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