Specific acquisition of functional CD59 but not CD46 or CD55 by hepatitis C virus.

Viruses of different families encode for regulators of the complement system (RCAs) or acquire such RCAs from the host to get protection against complement-mediated lysis (CML). As hepatitis C virus (HCV) shares no genetic similarity to any known RCA and is detectable at high titers in sera of infected individuals, we investigated whether HCV has adapted host-derived RCAs to resist CML. Here we report that HCV selectively incorporates CD59 while neither CD55, nor CD46 are associated with the virus. The presence of CD59 was shown by capture assays using patient- and cell culture-derived HCV isolates. Association of CD59 with HCV was further confirmed by Western blot analysis using purified viral supernatants from infected Huh 7.5 cells. HCV captured by antibodies specific for CD59 remained infectious for Huh 7.5 cells. In addition, blocking of CD59 in the presence of active complement reduced the titer of HCV most likely due to CML. HCV produced in CD59 knock-down cells were more significantly susceptible to CML compared to wild type virus, but neither replication, assembly nor infectivity of the virus seemed to be impaired in the absence of CD59. In summary our data indicate that HCV incorporates selectively CD59 in its envelope to gain resistance to CML in serum of infected individuals.

Emerging role for complement in HIV infection.

PURPOSE OF REVIEW: New evidence is provided that the complement system is not only an effective component of the innate immunity, but is also involved in bridging innate and adaptive immune response to control retroviral infections. RECENT FINDINGS: The complement contributes to the control of retroviral replication by various strategies, such as complement-mediated lysis, triggering of B-cell responses by trapping the virus on follicular dendritic cells in the germinal center or enhancing of antigen presentation and thus the induction of virus-specific cytotoxic T lymphocytes. HIV has evolved mechanisms to escape from complement-meditated neutralization and counteracts these immune responses by escaping from lysis, using follicular dendritic cells as anchor to generate a latent viral reservoir and enhancing the infection of antigen-presenting cells. SUMMARY: This review will discuss the complex interactions of complement and complement receptors with retroviruses and review the escape mechanisms, which protect this virus family from complement-mediated destruction.