Inhibition of complement-mediated cytolysis by the terminal complement inhibitor of XXXX .

@entity1 @entity537 @entity535 @entity1009 @entity784 @entity377 @entity4417 @entity1778 @entity4495 @entity4357
@entity537 ) is a lymphotropic herpesvirus that induces @entity784 and @entity1778 in New World primates other than its natural host, the squirrel monkey. @entity377 sequence analysis of the HVS genome revealed two open reading frames with significant homology to genes for @entity1 complement regulatory molecules. One of these genes encodes a predicted protein (designated HVSCD59) with 48% @entity535 sequence identity to the @entity1 terminal complement regulatory protein @entity1009 (HuCD59). The @entity1009 homolog from squirrel monkey (SMCD59) was cloned, and the corresponding @entity535 sequence showed 69% identity with HVSCD59. BALB/3T3 cells stably expressing HVSCD59, SMCD59, or HuCD59 were equally protected from complement-mediated lysis by human serum. However, only HVSCD59-expressing cells were effectively protected from complement-mediated lysis when challenged with rat serum, suggesting that HVSCD59 was less species restrictive. The complement regulatory activity of HVSCD59 and SMCD59 occurred after @entity4417 deposition, indicating terminal complement inhibition. Treatment of BALB/3T3 stable transfectants with @entity4357 -specific phospholipase C prior to complement attack decreased the complement regulatory function of HVSCD59, suggesting cell surface attachment via a @entity4495 anchor. Cells expressing HVSCD59 effectively inhibited complement-mediated lysis by squirrel monkey serum in comparison with SMCD59-expressing cells. Finally HVSCD59-specific transcripts were detected in owl monkey cells permissive for lytic HVS replication but not in T cells transformed by HVS, which failed to produce virions. These data are the first to demonstrate a functional, virally encoded terminal complement inhibitor and suggest that HVSCD59 represents a humoral immune evasion mechanism supporting the lytic life cycle of HVS.
