Infection-resistant monkeys could be crucial in the fight against HIV

Via Io9, by Alasdair Wilkins.

Sooty mangabeys are a monkey species found on the western coast of central Africa. Their unique immunity to SIV, a relative of HIV, has intrigued medical researchers for decades. Now we know just how their immunity works.

SIV and HIV function in much the same way - the viruses find two molecules on the surface of the cell, which are known as co-receptors. These molecules function much like gates. One of these molecules is CD4, which is found on immune cells known as T cells. The immune response triggered by the appearance of the virus stimulates these T cells, which boost the level of the other co-receptor, CCR5, which in turn facilitates the deadly infection.

But sooty mangabeys are able to avoid that chain of events, thanks to a unique type of T cell called a central memory T cell. When this particular type of T cell responds to the virus, it does so without activating CCR5. This helps the T cells survive the SIV infection, and it's a crucial reason why these monkeys are able to avoid the onset of AIDS. Best of all, central memory T cells are long-lived in the body, and their positioning in the lymph nodes makes them particularly effective in stopping the spread of SIV.

Emory University researcher Mirko Paiardini explains what this means:

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[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

HIV Envelope Discovery Could Reveal New Vaccine Targets

Via hivandhepatitis.com

An international study headed by a UC Davis scientist describes how a component of a potential HIV vaccine opens like a flower, undergoing one of the most dramatic protein rearrangements yet observed in nature.

The finding could reveal new targets for vaccines to prevent HIV infection and AIDS. A paper describing the work was published online this week in the journal Proceedings of the National Academy of Sciences.

In the new study, researchers from the U.S., Sweden and France explored the structure and behavior of the HIV envelope protein complex, which could potentially serve as a component of a vaccine aimed at eliciting the human immune system to generate antibodies against HIV.

"By opening up these less exposed regions, we might be able to raise more broadly cross-reactive antibodies to HIV," said R. Holland Cheng, professor of molecular and cellular biology at UC Davis and senior author of the study.

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[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

The Mystery of AIDS Immunity: Solved

From TIME Magazine, by Meredith Melnick

Bruce Walker, an AIDS researcher at Harvard University and Massachusetts General Hospital, has long been trying to understand why some people with HIV can remain untreated for decades and never progress to AIDS. On Nov. 4, Walker and colleagues published research that helps explain these HIV controllers: genetic variations that change key proteins in their immune systems.

The genetic variations change about a half-dozen amino acid building blocks; those variants make cells that are infected with HIV visible to the body's immune system and vulnerable to attack. NPR explained:

Five of the six variants are within a protein that controls how certain immune cells, called CD4s, display bits and pieces of viral protein on their outer shell- if they happen to be infected with a virus. HIV has a special affinity for infecting CD4 cells, and without constant antiviral treatment the virus slowly destroys the immune systems of most infected people.

But if a person has the newly discovered amino acid variants, his CD4 cells will be especially good at displaying pieces of HIV in a binding groove, or pocket of their outer coat. That enables killer cells, immune cells called CD8s, to target and kill the infected cells before they can spew forth more viruses.

For most people, the lack of these protective variants renders their HIV-infected cells invisible to their immune system.

Walker's team has also found these variants in people of European and African descent and in Hispanics. His team hopes their findings will help researchers figure out how to manipulate the immune response in people who do not have the benefit of the genetic variations.

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[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

Eradication of smallpox may have set the stage for HIV pandemic, study says

via Los Angeles Times, by Thomas H. Maugh II

"While these results are very interesting and hopefully may lead to a new weapon against the HIV pandemic, they are very preliminary and it is far too soon to recommend the general use of vaccinia immunization for fighting HIV," Weinstein said in a statement. Given the great difficulties researchers have encountered in trying to develop an HIV vaccine, the ironic fact is that we may once have had a vaccine that is more effective against the virus than anything that has since been developed, and we threw it away.

Laboratory tests suggest that immunity to smallpox triggered by the vaccinia (smallpox) vaccine can inhibit the replication of the AIDS virus. Such vaccination could have kept HIV transmission partially under control in the early days of the outbreak, but withdrawal of the smallpox vaccine in the 1950s would have freed it to spread unfettered, the researchers said.

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Theory Explains Why Some With HIV Survive Longer

via Physorg.com by, Jason Socrates Bardi

A group of researchers in Boston announced a new theory this week that may help to explain a longstanding mystery in AIDS research: why some people with HIV survive for decades without ever developing AIDS.

About one out of every 200 people who catch HIV are considered "long-term non-progressors" or "elite controllers" because they can live for many years with the virus without developing AIDS. Even the most sensitive tests often cannot detect the virus in their bloodstream.

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Microbicides, vaccines may need to repel HIV contact at mucosa

via Aidsmap News, by Keith Alcorn

Scientists have been faced with the question of how HIV actually gets underneath epithelial cells to infect other cells that are susceptible to HIV. "It's not the cells on top," Kaushic said. "It is the immune cells underneath that have all the receptors that HIV likes to latch on to and that allow the virus to replicate and establish infection. But it has to cross the epithelial barrier first!"

"This is a significant step forward in defining where prevention strategies, such as microbicides and vaccine, need to focus. Instead of trying to stop HIV from infecting the target cells underneath the epithelium, we need to think about ways to stop the virus from attaching to epithelial cells themselves," said Charu Kaushic.

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Unprotected sex between HIV-infected partners keeps immune responses activated

Crabb, Charlene

AIDS. 23(11):N7, July 17, 2009.

HIV acts as a ‘natural immunogen’, keeping anti-HIV-1 immune responses boosted in HIV-infected male couples who have unprotected sex, say University of California San Francisco researchers [original article from UCSF researchers: PLoS Pathog 2008; 4:e1000185].

Until now, little has been reported on the consequences of continued exposure to HIV in people who are already infected. But serosorting, the practice of identifying sexual partners based on their HIV status, is a growing trend. It often leads to unprotected sex between HIV infected individuals, which poses the risk of acquiring a drug-resistant strain of the virus.

To shed light on the immunological consequences of continued exposure to HIV, Christian Willberg and colleagues studied 49 men, from a San Francisco prospective cohort of couples in long-term relationships, who were suppressing their virus below the detection level (50RNAcopies/ml) with HAART. Twenty-nine men had partners whose virus was also in check due to antiviral therapy, whereas 20 men had viremic partners whose viral loads were more than 90 000RNAcopies/ml.

Using enzyme-linked immunosorbent spot (ELISPOT) assay to compare HIV-1-specific T-cell responses between the two groups, the researchers found significantly stronger (P¼0.001) responses against HIV-1 protease, reverse transcriptase, and integrase peptides in the men with viremic partners. The magnitude of their responses correlated with a greater frequency of unprotected sex, and in particular with the frequency of exposure through receptive (versus insertive) anal sex. No similar correlations were found in the men with nonviremic partners.

‘Rather than losing responses because their own virus has been suppressed by antiviral therapy,’ explains Willberg, ‘we found that the men are maintaining a response because they are constantly being exposed to their partner’s virus.’

That the amount of exposure drives the boosted HIV-1- specific immune responses was also illustrated in three individuals from the viremic partner group whose T-cell responses dropped significantly a year later. Two had partners who started antiretroviral therapy and were suppressing their viral loads. The third had reduced his exposure. (Seven individuals from the viremic partner group had blood samples available froma 1-year followup.)

The researchers note that superinfection is the most likely mechanism to maintain or boost the HIV-1 immune responses. However, HIV-1 sequencing of all participants in the study found no evidence of superinfection at the systemic level in which a new virus overgrows the existing strain. Willberg, who is now at Oxford University, cautions that the study’s phylogenetic analysis does not rule out localized superinfections in the gut, most likely the rectum.

Furthermore, no one knows whether maintaining a high T-cell response is good or bad. Willberg says that keeping an active HIV-1 immune response might help control viral rebound in a person when antiviral therapy fails for some reason, or it could indicate a compartmentalized superinfection and the increased risk of acquiring a drug-resistant strain. ‘It could be a double-edged sword,’ he says.