By Alix Morris
When a virus enters the body, the immune system launches a barrage of antibodies to stop the infection. In the case of HIV, however, the B cells that make those antibodies fail to generate a normal response, even in the early stages of infection, when concentrations of the virus are at their peak. Research published in the October 27th edition of Nature Immunology sheds some light on a potentially major driver of this dysfunction.
By Alix Morris
The perhaps biggest challenge to curing HIV infection is that the virus hides in latently infected, resting memory CD4+ T cells. These cells harbor integrated HIV DNA—the so-called provirus—in their genome, and unless they are activated to produce virus, they are indistinguishable from uninfected resting CD4+ T cells. One strategy to eradicate this reservoir is the so-called “kick and kill” approach: activate the latently infected cells so that they give themselves away by producing virus again, and then kill these virus-producing cells.
Some people infected with HIV can keep the level of virus in their blood in check without any treatment. In part, that’s because these so-called HV controllers carry specific variants of genes for HLA class I proteins, which are involved in the process by which virally infected cells tell specialized immune cells that they should be destroyed. Infected cells use these proteins to present HIV peptides to CD8+ T cells, and it appears that CD8+ T cells kill infected cells more efficiently when they are engaged by the protective variants, which are named B27 and B57. Some researchers believe that another reason for the better control of HIV infection is that when the virus mutates to escape the vigorous CD8+ T-cell attack induced by these variants, it pays a price: It doesn’t replicate very well anymore.
So the AIDS Vaccine conference in Barcelona started up today. And Day One went well, despite the forced absence of some leading scientists, owing to the shutdown of the US government over a budget impasse. Anthony Fauci, Director of the US National Institute of Allergy and Infectious Disease, participated via pre-recorded video, and spoke to journalists live.
HIV always seems to find a way around smartest strategies scientists cook up against it, and keeps coming up with surprises, the more researchers study it. Now cure researchers may well find that their understanding of how HIV hides in latently infected cells—the so-called HIV reservoir—may need to be adjusted, if a recent study is to be believed.
Could a vaccine be used to functionally cure HIV infection? New evidence from an animal study suggests the strategy may work, though the infection cleared was—of course—of simian immunodeficiency virus (SIV), not HIV.
Most HIV transmissions happen heterosexually, but so far, animal models don’t accurately recapitulate this process. Instead, researchers manually place a droplet of a solution that contains viruses inside the vagina of females.
When epidemiologists at the US Centers for Disease Control and Prevention (CDC) in Atlanta correctly suggested in 1982 that AIDS could be spread by blood transfusions, many blood bank officials reacted with skepticism. After all, the cause of AIDS was still a mystery, so there was no way to screen blood for the pathogen in question.
Given how fast two entirely new and deadly viruses—the H7N9 influenza strain in China and the MERS coronavirus in Saudi Arabia—were picked up by disease surveillance experts, we’ve been pondering how the tools and technologies we take for granted today might have altered the course of HIV and AIDS if they’d been available when AIDS blipped on the public health radar.
I attend a lot of scientific meetings. At the end of most, I ask participants what they thought were the highlights. But at this year’s 7th International AIDS Society conference on HIV Pathogenesis, Treatment and Prevention, held in Kuala Lumpur, Malaysia, from June 30th to July 3rd, I didn’t need to ask. The thing that had everybody excited was the announcement that researchers might have replicated the HIV cure achieved in Timothy Brown—the so-called Berlin patient.
The eradication of viral reservoirs remains among the most challenging obstacles to curing HIV infection, a problem that researchers have sought to solve by inducing HIV replication in latently infected, resting CD4+ T cells. The expectation is that the cells would then either die as a result of the renewed viral replication or become vulnerable to targeting by antiretroviral drugs or immune responses.
Most people assume, perhaps understandably, that HIV-infected injecting drug users (IDUs) are incapable of adhering to the daily grind of oral antiretroviral (ARV) treatment. Yet this assumption appears to be contradicted by the data. More than three dozen studies have shown IDUs are just as compliant as any other high-risk group in taking their antiviral pills every day.
Today was the last day of the first conference on vaccine design organized by Cold Spring Harbor (CSH) Asia, the Asian branch of the renowned Cold Spring Harbor conference in the state of New York. The gathering took place from June 3 to 7 at a brand new conference center and hotel built in 2010 in Suzhou, just one hour by car (half an hour by the recently constructed high speed train) from Shanghai. The center was built for CSH Asia to hold such meetings, said Maoyen Chi, who directs the CSH Asia program. So far, CSH Asia has held almost 40 meetings here, covering many areas of biology.
It was 30 years ago this month that researchers from the Pasteur Institute reported in Science the isolation of a new retrovirus from the lymphoid tissue of a gay Caucasian that appeared to be associated with AIDS-related syndromes.
IAVI Report readers might find this paper released by the Global Health Technologies Coalition interesting. It looks at the challenges faced by organizations working on solutions for diseases associated with poverty. The authors find that product development partnerships—a model for addressing public health needs that was recently covered in IAVI Report— play a central role in bringing together resources and the expertise of different sectors involved in related R&D. Yet there remain critical gaps in such efforts, the study finds--many associated with funding, regulatory processes, and the limited capacity for research and manufacturing in developing countries. The paper also looks at possible solutions to the identified obstacles.
It’s probably safe to say that the conference on “HIV Dynamics & Evolution”, in Utrecht, in the Netherlands, was somewhat unusual: It featured a lot of research involving HIV sequence analysis and mathematical modeling. And yes, many of the talks at the conference, which ended yesterday, came with differential equations (don’t worry, I won’t get into that in this post.)