As people around the globe mark World AIDS Day, researchers continue to grapple with a disease for which there are treatments but no known cure.
Some believe that defeating a scourge as cunning as HIV requires an innovative solution, which is why two Canadian researchers have been given funding to explore radical theories about how to kill HIV-infected cells.
“The virus mutates, so it’s not like there’s a stable object there, so that for 10 years we know what the stable object is and we can keep doing research on this thing we call HIV,” says Peter A. Newman, Research Chair for Health and Social Justice at the University of Toronto.
“The virus is constantly mutating, so in talking about vaccines, for example, it’s very difficult to know how to target it.”
According to a 2010 report by the United Nations, about 33 million people worldwide are living with HIV/AIDS — two-thirds of them in sub-Saharan Africa. While an increasing number are receiving treatment, there is no vaccine as yet.
Last month, the Bill and Melinda Gates Foundation announced that Andrès Finzi, a researcher at the Centre Hospitalier de l’Université de Montréal, and Mario Ostrowski, an infectious disease consultant in Toronto, had each won a $100,000 grant for their research into killing HIV, the virus that causes acquired immunodeficiency syndrome (AIDS).
The goal of the HIV virus is to go into human cells, replicate itself and then infect other cells. To do so, it has developed a unique "key" called envelope glycoprotein, which attaches to a lock called CD4 to gain access into human cells.
Finzi's lab is trying to understand how the key on HIV particles works and, as he puts it, “mettre un baton dans la roue,” a French expression that means throwing a wrench in the works. More specifically, he hopes to block the HIV virus from even attaching to human cells.
Originally from Patagonia, Argentina, Finzi opened his lab in Montreal in September 2011, after spending four years doing his post-doctoral work at Harvard.
In his submission to the Gates Foundation, Finzi proposed killing HIV cells through a Trojan horse method he calls “reverse fusion.” In this experimental process, Finzi’s lab would create toxic viral particles that have the lock, rather than the key, and thus would attack HIV-infected cells. Once these cells bound themselves to the toxic particles, the toxic particles would deliver toxic genes that would kill the HIV-infected cells.
“I have done work in the lab that says this concept works, but now I’ve got the support to be able to push this idea forward, to see if we can really kill the cells,” says Finzi.
“This phase of the grant is just a proof of concept: are we specifically able to kill HIV infected cells? We need to do that in a way that’s not going to harm other cells.”
Hide and seek
Ostrowski’s lab, meanwhile, is looking at ways to boost the immune system’s ability to detect HIV.
People diagnosed with HIV are currently treated with a “cocktail” of anti-retroviral drugs. One of the inherent snags is that patients must stay on the treatment for life; if they go off it, the HIV virus runs amok in the body again. That’s because the ever-mutating virus has a way of hiding out in parts of the body where the immune system cannot detect it — in what are known as virus reservoirs.
Ostrowski is looking to help the immune system suss out and kill these fugitive virus particles.
“The way immune cells kill virus-infected cells is through something called a killer cell,” says Ostrowski. “When the immune system makes these killer cells, they can recognize virus antigens on the surface of an infected cell, and eliminate the virus from the body. However, HIV can mutate and escape recognition by the killer cells.”
So how would these killer cells find the elusive HIV virus?
As Ostrowski points out, up to 40 per cent of our chromosomes contain codes for DNA left over from extinct, million-year-old viruses, and about eight per cent of our DNA is from a virus similar to HIV, known as human endogenous retrovirus (HERV). Why it’s there remains a scientific mystery, but Ostrowski's group has learned that when a human cell is infected with HIV, that same cell also starts showing proteins from these ancient viruses.
In taking immune cells from an HIV-infected person, Ostrowski’s team discovered a killer cell that could detect these HERV proteins. This is key, because the HERV proteins can't mutate like HIV does. So for the Gates grant, Ostrowski proposed creating a vaccine that would force the immune system to target these HERV proteins and attack those HIV-infected cells, in the hopes of getting rid of the HIV reservoir.
Ostrowski’s team will take these killer cells and expand their numbers in test tubes.
“Then we’ll add them to cells that are infected with HIV, and we’re going to see if these killer cells can completely eradicate the virus in tissue culture.”
Funding the unconventional
Finzi and Ostrowski’s projects are among 15 proposals to receive money from the Gates Foundation for HIV research. According to Michal Fishman, a senior communications officer for the foundation, there were 398 submissions for this topic in this round of funding.
Launched in 1994, the foundation is dedicated to enhancing healthcare and reducing extreme poverty around the world. Through its Grand Challenges in Global Health initiative, the foundation finances medical research of a decidedly radical nature.
“The funding is really based on the idea itself,” says Fishman, who says that Finzi and Ostrowski have the next 12 to 18 months “to prove their hypothesis.”
If the results are favourable, the Gates Foundation will give them an additional $1 million for a second phase of research.
Ostrowski says that private endowments like the Gates grants can further ideas more quickly than government grants, which often require preliminary data that can take years to accumulate.
Newman says that this insistence on data can often work against innovation.
“The most innovative ideas are things that are outside the box or are using ways of approaching a problem or issue that haven’t been tested before,” says Newman.