Send to

Choose Destination
Viral Immunol. 2008 Dec;21(4):469-76. doi: 10.1089/vim.2008.0032.

Complement component C1q and anti-hexon antibody mediate adenovirus infection of a CAR-negative cell line.

Author information

Department of Pharmacology, Canji Inc., San Diego, California, USA.


Realization of the potential clinical utility of recombinant adenovirus for gene therapy or vaccine development depends on a better understanding of the role of naturally occurring or therapy-induced anti-adenovirus antibodies. This study addresses the impact of anti-adenovirus neutralizing antibodies and the complement protein C1q on adenovirus infection of coxsackie and adenovirus receptor (CAR)-positive, and especially CAR-negative cells. Initially, transduction efficiency of adenovirus vectors was assessed in the presence or absence of human sera derived from healthy individuals that were seropositive for anti-adenovirus neutralizing antibodies. Infection was monitored by transgene expression in vitro using a replication-deficient adenovirus encoding green fluorescent protein (Ad-GFP). HeLa cells (CAR-positive) were readily infected by Ad-GFP and increasing concentrations of pooled sera increasingly inhibited infection. In contrast, rhabdomyosarcoma (RD) cells, a CAR-negative cell, were poorly infected by Ad-GFP. However, in the presence of human serum, robust GFP expression was observed. This expression was completely abrogated if the human serum was heat-inactivated. Addition of purified human C1q protein to the heat-inactivated serum restored GFP expression. Similar results were seen when human C1q protein was added to purified anti-hexon antibodies, but not to anti-fiber or anti-penton base antibodies, thus implicating anti-hexon antibodies as the infective antibody component of the human sera. These studies suggest that complement protein C1q and anti-hexon antibodies together can mediate efficient adenovirus infection in CAR-negative cell types.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center