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Red and green depict the part of the HIV envelope protein that mutated in two patients (185F and 205F) in response to pressure from their immune systems. The rest of the envelope protein is blue.

EMORY (US)—HIV’s ability to mutate in response to immune system pressure means the virus can take several escape routes from antibodies, eventually exhausting the immune system, new research shows.

While the human immune system has the ability to temporarily overpower HIV in early infection, say Emory University researchers, the virus eventually wins out.

Most newly infected patients develop neutralizing antibodies—blood proteins that glob onto the virus—that would allow patients to defend themselves—if they were facing only one target.

HIV2

The team’s results suggest that if a vaccine component that can stimulate neutralizing antibodies can be identified, HIV’s capacity for rapid mutation could still be a confounding factor.

A single type of neutralizing antibody may not be enough to contain HIV, says senior author Cynthia Derdeyn, associate professor of pathology.

“These neutralizing antibodies work really well—they hit the virus fast and hard,” she says. “But so far, every time we look, the virus escapes.”

Derdeyn and her colleagues collaborated with a public health program directed by Susan Allen, professor of global health, that enrolls heterosexual couples with one HIV-positive partner in Zambia. The program provides thousands of couples counseling and condom supplies every three months. Despite these measures, a low level of HIV transmission still occurs.

The team took blood samples a few weeks after infection occurred and then later as two participants’ immune responses continued. Individual viruses over the first two years of HIV infection were isolated and tested to see how well the patients’ own antibodies could neutralize them.

“In one patient where we had very early samples, there was evidence that neutralizing antibody came up within weeks, and that’s earlier than what was previously thought,” Derdeyn says.

The initially infecting virus starts off homogenous because of a “genetic bottleneck” effect.

In both patients, some viruses mutated part of their outer proteins so that after the mutation, an enzyme would be likely to attach a sugar molecule to it. The sugar interferes with antibody attack. However this tactic, known as the “glycan shield,” was not observed in all cases.

Other viruses mutated the part of the outer protein that the neutralizing antibodies stick to directly. In both patients, many changes in the virus’ genetic code were necessary for escape.

“We need to understand early events in the immune response if we are going to figure out what a potential vaccine should have in it,” Derdeyn says. “What we can show is that even in one patient, several escape strategies are going on.”

That means that in order to be immune to HIV infection, someone may need to have several types of neutralizing antibodies ready to go. Seeing how the virus mutates will allow researchers to choose the best parts to put in a vaccine, she says.

A companion paper in the same issue of PLOS Pathogens from South African researchers demonstrates similar cycles of neutralizing antibody attack and escape.

The research, which appears online and in the September issue of the Public Library of Scientific Pathogens, was supported by the National Institutes of Health and The Bill and Melinda Gates Foundation.

Emory University news: www.emory.edu/home/news/