HIV-1 damages gut antibody producing immune cells within days of infection

Jul 07, 2009
Peyer's Patches in the intestine. Image: Huck Finne, via Wikipedia

The virus that causes AIDS is classified as a lentivirus, a word derived from the Latin prefix, "lenti-," meaning "slow." But new research from the NIAID-funded Center for HIV/AIDS Vaccine Immunology suggests that HIV-1 is anything but - moving at breathtaking speed in destroying and dysregulating the body's gut-based B-cell antibody-producing system.

"These new data show that damage to the antibody arm of the begins quickly, within days. We know that by 80 days, half of the generative microenvironments for antibodies within the immune system in the gut are destroyed," said Barton Haynes, M.D., director of the Center for HIV/AIDS Vaccine Immunology and the senior author of the study.

The study, published in the open access journal at
http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.1000107, is the first to examine what happens to B cells in the gut in the earliest stage of HIV-1 infection. Researchers say the findings may shed light on one of the big mysteries in : why the , or antibody response, is so slow to arise - and so weak when it finally does, that it is unable to offer any kind of meaningful defense.

B cells that make antibodies against invading microbes are born in the bone marrow but migrate out and mature in different locations throughout the body. Some wind up in the intestine and settle in stretches of lymph node-like follicles called Payer's patches that are found at the bottom of the small intestine.

There, tucked inside the follicles' nurturing germinal centers, the B cells set up surveillance, waiting to rise up against incoming bacteria, viruses, or other pathogens. "Unfortunately, we found they are no match for HIV-1," said Anthony Moody, M.D. a member of the Duke Human Vaccine Institute (DHVI) and a lead author of the study.

Moody and co-lead author Marc Levesque, M.D., a former member of DHVI but now at the University of Pittsburgh, led a team of researchers in examining B cells in blood as early as 17 days after viral transmission, and in lymph tissue in the gut beginning at 47 days after transmission in 40 people infected with HIV-1. They compared their findings with similar tissue from healthy controls.

They discovered that even at this early stage, HIV-1 had already ravaged the gut's B cell arm of the immune system. The vast majority of the follicles in the Payer's patches had been damaged. "HIV-1 turns on the immune system, but turns it on in the wrong way," Moody said. "We found that it was churning out all sorts of B cells. Some appeared to be reactive against HIV-1, but others appeared reactive to things like influenza as well as self molecules."

In addition, the researchers found that by as early as 17 days after transmission, HIV-1 decreased the numbers of naďve B cells - cells that may have had the potential to mature into potent infection-fighters.

Such deregulation had been described in chronic HIV-1-infection, but never before in such an early phase of the disease, said Moody. "It is no wonder the B cell response is so weak in response to HIV-1 infection. The causes such early disruption that it is simply not able to work as it is supposed to. "It is really quite sobering."

The findings may be sobering, but they also reinforce the research team's vision of what a successful vaccine might look like.

"First, an effective vaccine will have to produce potent that would already be in circulation before infection occurs," said Haynes, who is also a professor of medicine and director of the Human Vaccine Institute at Duke. "Then, if the virus manages to escape that first line of defense, the vaccine would need to be able to educate the immune system to rapidly respond to eliminate transmitted virus strains. It is this continually emerging picture of what happens at the very earliest period after infection that is helping us to understand the job we have to do," Haynes said.

Source: Duke University Medical Center (news : web)

Explore further: Linking the microbial and immune environment in semen to HIV viral load and transmission

add to favorites email to friend print save as pdf

Related Stories

Scientists Find Rare, Potent Antibody to HIV-1

Feb 23, 2009

(PhysOrg.com) -- Scientists at Duke University Medical Center have for the first time isolated an important antibody in human serum that could potentially play a key role in the design of an AIDS vaccine. The research appears ...

How HIV vaccine might have increased odds of infection

Nov 03, 2008

In September 2007, a phase II HIV-1 vaccine trial was abruptly halted when researchers found that the vaccine may have promoted, rather than prevented, HIV infection. A new study by a team of researchers at the Montpellier ...

HIV conquers immune system faster than previously realized

Jul 18, 2008

New research into the earliest events occurring immediately upon infection with HIV-I shows that the virus deals a stunning blow to the immune system earlier than was previously understood. According to scientists at Duke ...

HIV isolate from Kenya provides clues for vaccine design

Jan 02, 2008

Two simple changes in its outer envelope protein could render the AIDS virus vulnerable to attack by the immune system, according to research from Kenya and the Fred Hutchinson Cancer Research Center published in PLoS Medicine.

Exhausted B cells fail to fight HIV

Jul 14, 2008

HIV tires out the cells that produce virus-fighting proteins known as antibodies, according to a human study that will be published online July 14 in the Journal of Experimental Medicine.

Recommended for you

User comments : 0