2, 5, 6 Similarly, these two proteins also provide resistance for HIV-1-infected cells from ADCML by sera from HIV-1-infected patients.8 Blocking CD55 or CD59 function

with specific Abs or removing these molecules by treatment of phosphatidylinositol-specific phospholipase C (PI-PLC), a protein enzyme used for release of GPI-APs from selleck cell membrane, renders virions and infected cells sensitive to complement attack.2, 5, 6, 8 HCV is an enveloped positive-sense single-stranded RNA virus of the family Flaviviridae. Similar to HIV-1 infection, Abs against a wide variety of both HCV structural and nonstructural (NS) protein epitopes become detectable within weeks postinfection.9, 10 Patients who become chronically infected develop high-titer and crossreactive nAbs,9 yet fail to clear the virus. It is unknown whether HCV virions also incorporate RCA to protect against ADCML. HCV particles have been found to contain many host lipoproteins11, 12 which play important Apitolisib purchase roles in the HCV life cycle at various stages.13 In fact, the cellular lipid droplet has been shown to be an important organelle for HCV production, as inhibition of lipid biosynthesis

efficiently blocks HCV replication.14 HCV particles bind to specific cell-surface proteins (CD81, SR-B1, low density lipoprotein receptor, glycosaminoglycans, CD209, and CD209 ligand) to trigger virus internalization by clathrin-dependent endocytosis.15 HCV translation is then initiated to produce a single polyprotein that is cleaved by cellular and viral proteases into 10 small proteins including three structural proteins

(Core, E1, and E2), and seven NS proteins (P7, NS2, NS3, NS4A, NS4B, NS5A, and Etomidate NS5B).16, 17 Viral RNA replication takes place in a membrane-associated replication complex (the membranous web) that consists of viral NS proteins, replicating RNA, and cellular membranes.17 The newly synthesized viral genomes bud into the endoplasmic reticulum (ER) lumen to form viral particles. Thus, the ER plays a critical role in formation of HCV envelope and viral maturation, although the molecular mechanism of this is not fully understood. The ER also plays a central part in the synthesis and modification of GPI-APs such as CD59 in all eukaryotic cells.18 Therefore, it is possible for HCV to encounter and obtain CD59 and other GPI-APs in the ER and other cellular organelles. The current study was undertaken to determine whether HCV virions incorporate CD59 into the viral Env at biologically functional levels. The results indicate that CD59 is incorporated into both cell line-derived and plasma primary HCV virions at levels that protect against ADCML. This is the first demonstration that HCV virions contain and hijack RCA proteins to escape the humoral immune response.