Cell Host & Microbe paper implicates C1q but also provides evidence of other immune factors that are at play.

Researchers at Washington University School of Medicine say that a controversial phenomenon known as antibody-dependent enhancement (ADE) of infection is suppressed by C1q, a blood-borne immune system compound.

In the 1960s, according to the investigators, epidemiological studies of dengue fever showed that patients who had beaten the virus once could be more vulnerable to it when they became infected again with a related but not identical strain.

Scientists theorized, based on experiments in cell cultures, that the vulnerable patients didn’t have adequate antibodies to eradicate the virus when it returned. They believed that the virus was somehow taking advantage of the antibodies and using them to accelerate infection. When researchers tried to simulate the phenomenon in animal models, however, they could not.

In the current study, the Washington Univ. team conducted an ADE test. Instead of using stored blood sera, they took fresh sera from mice and applied it to dengue virus and therapeutic antibodies for dengue. Fresh, unheated sera blocked ADE, while heated sera did not, the scientists report. They speculate that this was due to a lack of complements in the heated blood.

The complement system, a family of immune compounds that normally circulate in the bloodstream, is activated when the immune system detects an invader and transforms them into inhibitors against the invader.

The team next tested sera from several different lines of mice, each genetically engineered to be missing one component of the complement system. Only sera from mice missing C1q led to ADE in cell cultures, they say. When the investigators added purified C1q to the virus and antibodies, it reportedly blocked ADE.

The researchers found evidence in follow-up experiments, though, that other immune factors affect the chances that ADE will occur.

The study is published in Cell Host & Microbe.

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